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Population genomics of Klebsiella pneumoniae

  • 1.

    Adeolu, M., Alnajar, S., Naushad, S. & Gupta, R. S. Genome-based phylogeny and taxonomy of the ‘Enterobacteriales’: proposal for Enterobacterales ord. nov. divided into the families Enterobacteriaceae, Erwiniaceae fam. nov., Pectobacteriaceae fam. nov., Yersiniaceae fam. nov., Hafniaceae fam. nov., Morganellaceae fam. nov., and Budviciaceae fam. nov. Int. J. Syst. Evol. Microbiol. 66, 5575–5599 (2016).

    • Google Scholar
  • 2.

    Pendleton, J. N., Gorman, S. P. & Gilmore, B. F. Clinical relevance of the ESKAPE pathogens. Expert. Rev. Anti Infect. Ther. 11, 297–308 (2013).

    • Google Scholar
  • 3.

    Okomo, U. et al. Aetiology of invasive bacterial infection and antimicrobial resistance in neonates in sub-Saharan Africa: a systematic review and meta-analysis in line with the STROBE-NI reporting guidelines. Lancet Infect. Dis. 19, 1219–1234 (2019).

    • Google Scholar
  • 4.

    Zaidi, A. K. M. et al. Hospital-acquired neonatal infections in developing countries. Lancet 365, 1175–1188 (2005).

    • Google Scholar
  • 5.

    World Health Organization. Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery, and Development of New Antibiotics (WHO, 2017).

  • 6.

    Cassini, A. et al. Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis. Lancet Infect. Dis. 19, 56–66 (2019).

    • Google Scholar
  • 7.

    Musicha, P. et al. Trends in antimicrobial resistance in bloodstream infection isolates at a large urban hospital in Malawi (1998–2016): a surveillance study. Lancet. Infect. Dis. 17, 1042–1052 (2017).

    • Google Scholar
  • 8.

    Bagley, S. T. Habitat association of Klebsiella species. Infect. Contr. 6, 52–58 (1985).

    • Google Scholar
  • 9.

    Holt, K. E. et al. Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health. Proc. Natl Acad. Sci. USA 112, E3574–E3581 (2015). This large-scale comparative genomics study of diverse K. pneumoniae and related members of the species complex from seven countries establishes the global genomic framework and the scale and heterogeneity of the pan-genome, and identifies genetic loci that are statistically associated with invasive disease versus asymptomatic colonization in humans.

    • Google Scholar
  • 10.

    Wyres, K. L. et al. Distinct evolutionary dynamics of horizontal gene transfer in drug resistant and virulent clones of Klebsiella pneumoniae. PLoS Genet. 15, e1008114 (2019).

    • Google Scholar
  • 11.

    Gu, D. et al. A fatal outbreak of ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae in a Chinese hospital: a molecular epidemiological study. Lancet Infect. Dis. 3099, 1–10 (2017). This study presents an initial report of MDR-ST11 harbouring a KpVP-1 virulence plasmid variant, which displays enhanced survival in a human neutrophil assay and enhanced virulence in the Galleria mellonella infection model in comparison with typical MDR-ST11.

    • Google Scholar
  • 12.

    Lam, M. M. C. et al. Convergence of virulence and MDR in a single plasmid vector in MDR Klebsiella pneumoniae ST15. J. Antimicrob. Chemother. 74, 1218–1222 (2019).

    • Google Scholar
  • 13.

    Long, S. W. et al. Whole-genome sequencing of human clinical Klebsiella pneumoniae isolates reveals misidentification and misunderstandings of Klebsiella pneumoniae, Klebsiella variicola, and Klebsiella quasipneumoniae. mSphere 2, e00290–e00317 (2017).

    • Google Scholar
  • 14.

    Gorrie, C. L. et al. Gastrointestinal carriage is a major reservoir of K. pneumoniae infection in intensive care patients. Clin. Infect. Dis. 65, 208–215 (2017).

    • Google Scholar
  • 15.

    Rodrigues, C., Passet, V., Rakotondrasoa, A. & Brisse, S. Identification of Klebsiella pneumoniae, Klebsiella quasipneumoniae, Klebsiella variicola and related phylogroups by MALDI-TOF mass spectrometry. Front. Microbiol. 9, 1–7 (2018).

    • Google Scholar
  • 16.

    Long, S. W. et al. Population genomic analysis of 1,777 extended-spectrum β-lactamase-producing Klebsiella pneumoniae isolates, Houston, Texas: unexpected abundance of clonal group 307. mBio 8, e00489–e00517 (2017).

    • Google Scholar
  • 17.

    Henson, S. P. et al. Molecular epidemiology of Klebsiella pneumoniae invasive infections over a decade at Kilifi County Hospital in Kenya. Int. J. Med. Microbiol. 307, 422–429 (2017).

    • Google Scholar
  • 18.

    Heinz, E. et al. Resistance mechanisms and population structure of highly drug resistant Klebsiella in Pakistan during the introduction of the carbapenemase NDM-1. Sci. Rep. 9, 2392 (2019).

    • Google Scholar
  • 19.

    Gorrie, C. L. et al. Antimicrobial resistant Klebsiella pneumoniae carriage and infection in specialized geriatric care wards linked to acquisition in the referring hospital. Clin. Infect. Dis. 67, 161–170 (2018).

    • Google Scholar
  • 20.

    Wyres, K. L. & Holt, K. E. Klebsiella pneumoniae as a key trafficker of drug resistance genes from environmental to clinically important bacteria. Curr. Opin. Microbiol. 45, 131–139 (2018).

    • Google Scholar
  • 21.

    Marques, C. et al. Evidence of Klebsiella pneumoniae sharing between healthy companion animals and co-habiting humans. J. Clin. Microbiol. 57, e01537–e01618 (2019).

    • Google Scholar
  • 22.

    Zadoks, R. N. et al. Sources of Klebsiella and Raoultella species on dairy farms: be careful where you walk. J. Dairy Sci. 94, 1045–1051 (2011).

    • Google Scholar
  • 23.

    Conlan, S., Kong, H. H. & Segre, J. A. Species-level analysis of DNA sequence data from the NIH human microbiome project. PLoS One 7, e47075 (2012).

    • Google Scholar
  • 24.

    Martin, R. M. et al. Molecular epidemiology of colonizing and infecting isolates of Klebsiella pneumoniae. mSphere 1, e00261–e00316 (2016).

    • Google Scholar
  • 25.

    Ludden, C. et al. A One Health study of the genetic relatedness of Klebsiella pneumoniae and their mobile elements in the East of England. Clin. Infect. Dis. 70, 219–226 (2020).

    • Google Scholar
  • 26.

    Chung, D. R. et al. Fecal carriage of serotype K1 Klebsiella pneumoniae ST23 strains closely related to liver abscess isolates in Koreans living in Korea. Eur. J. Clin. Microbiol. Infect. Dis. 31, 481–486 (2012).

    • Google Scholar
  • 27.

    Lin, Y.-T. et al. Seroepidemiology of Klebsiella pneumoniae colonizing the intestinal tract of healthy Chinese and overseas Chinese adults in Asian countries. BMC Microbiol. 12, 13 (2012).

    • Google Scholar
  • 28.

    Löhr, I. H. et al. Long-term faecal carriage in infants and intra-household transmission of CTX-M-15-producing Klebsiella pneumoniae following a nosocomial outbreak. J. Antimicrob. Chemother. 68, 1043–1048 (2013).

    • Google Scholar
  • 29.

    Mo, Y. et al. Carriage duration of carbapenemase-producing Enterobacteriaceae in a hospital cohort—implications for infection control measures. medRxiv. https://doi.org/10.1101/19001479 (2019).

    • Google Scholar
  • 30.

    Podschun, R. & Ullmann, U. Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin. Microbiol. Rev. 11, 589–603 (1998).

    • Google Scholar
  • 31.

    Shimasaki, T. et al. Increased relative abundance of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae within the gut microbiota is associated with risk of bloodstream infection in long-term acute care hospital patients. Clin. Infect. Dis. 68, 2053–2059 (2019).

    • Google Scholar
  • 32.

    Xu, L., Sun, X. & Ma, X. Systematic review and meta-analysis of mortality of patients infected with carbapenem-resistant Klebsiella pneumoniae. Ann. Clin. Microbiol. Antimicrob. 16, 18 (2017).

    • Google Scholar
  • 33.

    Bassetti, M., Peghin, M., Vena, A. & Giacobbe, D. R. Treatment of infections due to MDR Gram-negative bacteria. Front. Med. 6, 74 (2019).

    • Google Scholar
  • 34.

    Manohar, P., Tamhankar, A. J., Lundborg, C. S. & Nachimuthu, R. Therapeutic characterization and efficacy of bacteriophage cocktails infecting Escherichia coli, Klebsiella pneumoniae, and Enterobacter species. Front. Microbiol. 10, 574 (2019).

    • Google Scholar
  • 35.

    Meatherall, B. L., Gregson, D., Ross, T., Pitout, J. D. D. & Laupland, K. B. Incidence, risk factors, and outcomes of Klebsiella pneumoniae bacteremia. Am. J. Med. 122, 866–873 (2009).

    • Google Scholar
  • 36.

    Russo, T. A. & Marr, C. M. Hypervirulent Klebsiella pneumoniae. Clin. Microbiol. Rev. 32, e00001–e00019 (2019).

    • Google Scholar
  • 37.

    Ko, W. C. et al. Community-acquired Klebsiella pneumoniae bacteremia: global differences in clinical patterns. Emerg. Infect. Dis. 8, 160–166 (2002).

    • Google Scholar
  • 38.

    Kim, J. K., Chung, D. R., Wie, S. H., Yoo, J. H. & Park, S. W. Risk factor analysis of invasive liver abscess caused by the K1 serotype Klebsiella pneumoniae. Eur. J. Clin. Microbiol. Infect. Dis. 28, 109–111 (2009).

    • Google Scholar
  • 39.

    Brockhurst, M. A. et al. The ecology and evolution of pangenomes. Curr. Biol. 29, R1094–R1103 (2019).

    • Google Scholar
  • 40.

    Bialek-Davenet, S. et al. Genomic definition of hypervirulent and multidrug-resistant Klebsiella pneumoniae clonal groups. Emerg. Infect. Dis. 20, 1812–1820 (2014). This work establishes the cgMLST scheme for K. pneumoniae and the associated species complex, which is based on 694 core genes and is available through the BIGSdb-Kp online database.

    • Google Scholar
  • 41.

    Diancourt, L., Passet, V., Verhoef, J., Grimont, P. A. & Brisse, S. Multilocus sequence typing of Klebsiella pneumoniae nosocomial isolates. J. Clin. Microbiol. 43, 4178–4182 (2005).

    • Google Scholar
  • 42.

    Brisse, S. et al. Virulent clones of Klebsiella pneumoniae: identification and evolutionary scenario based on genomic and phenotypic characterization. PLoS One 4, e4982 (2009).

    • Google Scholar
  • 43.

    Breurec, S. et al. Klebsiella pneumoniae resistant to third-generation cephalosporins in five African and two Vietnamese major towns: multiclonal population structure with two major international clonal groups, CG15 and CG258. Clin. Microbiol. Infect. 19, 349–355 (2013).

    • Google Scholar
  • 44.

    McInerney, J. O., McNally, A. & O’Connell, M. J. Why prokaryotes have pangenomes. Nat. Microbiol. 2, 17040 (2017).

    • Google Scholar
  • 45.

    Wyres, K. L. et al. Extensive capsule locus variation and large-scale genomic recombination within the Klebsiella pneumoniae clonal group 258. Genome Biol. Evol. 7, 1267–1279 (2015).

    • Google Scholar
  • 46.

    Lam, M. M. C. et al. Population genomics of hypervirulent Klebsiella pneumoniae clonal group 23 reveals early emergence and rapid global dissemination. Nat. Commun. 9, 2703 (2018).

    • Google Scholar
  • 47.

    Bowers, J. R. et al. Genomic analysis of the emergence and rapid global dissemination of the clonal group 258 Klebsiella pneumoniae pandemic. PLoS One 10, e0133727 (2015).

    • Google Scholar
  • 48.

    Navon-Venezia, S., Kondratyeva, K. & Carattoli, A. Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance. FEMS Microbiol. Rev. 41, 252–275 (2017).

    • Google Scholar
  • 49.

    Conlan, S. et al. Plasmid dynamics in KPC-positive Klebsiella pneumoniae during long-term patient colonization. mBio 7, e00742–e00816 (2016).

    • Google Scholar
  • 50.

    Shen, J., Lv, L., Wang, X., Xiu, Z. & Chen, G. Comparative analysis of CRISPR–Cas systems in Klebsiella genomes. J. Basic. Microbiol. 57, 325–336 (2017).

    • Google Scholar
  • 51.

    Ellington, M. J. et al. Contrasting patterns of longitudinal population dynamics and antimicrobial resistance mechanisms in two priority bacterial pathogens over 7 years in a single center. Genome Biol. 20, 184 (2019).

    • Google Scholar
  • 52.

    Wyres, K. L. & Holt, K. E. Klebsiella pneumoniae population genomics and antimicrobial-resistant clones. Trends Microbiol. 24, 944–956 (2016).

    • Google Scholar
  • 53.

    Wyres, K. L. et al. Emergence and rapid global dissemination of CTX-M-15-associated Klebsiella pneumoniae strain ST307. J. Antimicrob. Chemother. 74, 577–581 (2019).

    • Google Scholar
  • 54.

    David, S. et al. Epidemic of carbapenem-resistant Klebsiella pneumoniae in Europe is driven by nosocomial spread. Nat. Microbiol. 4, 1919–1929 (2019). This study is a genomic analysis of >1,700 CRKp and carbapenem-susceptible K. pneumoniae infections isolated from patients in 244 hospitals in 32 countries across Europe, providing the first large-scale systematic sample for comparison of clone and resistance gene distributions.

    • Google Scholar
  • 55.

    Turton, J. F. et al. Virulence genes in isolates of Klebsiella pneumoniae from the UK during 2016, including among carbapenemase gene-positive hypervirulent K1-ST23 and ‘non-hypervirulent’ types ST147, ST15 and ST383. J. Med. Microbiol. 67, 118–128 (2017).

    • Google Scholar
  • 56.

    Siu, L. K. et al. Molecular typing and virulence analysis of serotype K1 Klebsiella pneumoniae strains isolated from liver abscess patients and stool samples from noninfectious subjects in Hong Kong, Singapore, and Taiwan. J. Clin. Microbiol. 49, 3761–3765 (2011).

    • Google Scholar
  • 57.

    Lin, J. C. et al. Genotypes and virulence in serotype K2 Klebsiella pneumoniae from liver abscess and non-infectious carriers in Hong Kong, Singapore and Taiwan. Gut Pathog. 12, 21 (2014).

    • Google Scholar
  • 58.

    Shi, Q. et al. Diversity of virulence level phenotype of hypervirulent Klebsiella pneumoniae from different sequence type lineage. BMC Microbiol. 18, 1–6 (2018).

    • Google Scholar
  • 59.

    Lee, I. R. et al. Differential host susceptibility and bacterial virulence factors driving Klebsiella liver abscess in an ethnically diverse population. Sci. Rep. 13, 29316 (2016).

    • Google Scholar
  • 60.

    Zhang, Y. et al. High prevalence of hypervirulent Klebsiella pneumoniae infection in China: geographic distribution, clinical characteristics, and antimicrobial resistance. Antimicrob. Agents Chemother. 60, 6115–6120 (2016).

    • Google Scholar
  • 61.

    Wyres, K. L. et al. Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia. Genomic med. 12, 11 (2019).

    • Google Scholar
  • 62.

    Heinz, E., Brindle, R., Morgan-McCalla, A., Peters, K. & Thomson, N. R. Caribbean multi-centre study of Klebsiella pneumoniae: whole genome sequencing, antimicrobial resistance and virulence factors. Microb. Genomics. 5, e000266 (2019).

    • Google Scholar
  • 63.

    Musicha, P. et al. Genomic analysis of Klebsiella pneumoniae isolates from Malawi reveals acquisition of multiple ESBL determinants across diverse lineages. J. Antimicrob. Chemother. 74, 1223–1232 (2019).

    • Google Scholar
  • 64.

    Zhang, R. et al. Presence of NDM in non-E. coli Enterobacteriaceae in the poultry production environment. J. Antimicrob. Chemother. 74, 2209–2213 (2019).

    • Google Scholar
  • 65.

    Marques, C. et al. Klebsiella pneumoniae causing urinary tract infections in companion animals and humans: population structure, antimicrobial resistance and virulence genes. J. Antimicrob. Chemother. 74, 594–602 (2019).

    • Google Scholar
  • 66.

    Anzai, E. K. et al. First case report of non-human primates (Alouatta clamitans) with the hypervirulent Klebsiella pneumoniae serotype K1 strain ST23: a possible emerging wildlife pathogen. J. Med. Primatol. 46, 337–342 (2017).

    • Google Scholar
  • 67.

    Bowring, B. G., Fahy, V. A., Morris, A. & Collins, A. M. An unusual culprit: Klebsiella pneumoniae causing septicaemia outbreaks in neonatal pigs? Vet. Microbiol. 203, 267–270 (2017).

    • Google Scholar
  • 68.

    Runcharoen, C. et al. Whole genome sequencing reveals high-resolution epidemiological links between clinical and environmental Klebsiella pneumoniae. Genome Med. 9, 6 (2017).

    • Google Scholar
  • 69.

    Davis, G. S. et al. Intermingled Klebsiella pneumoniae populations between retail meats and human urinary tract infections. Clin. Infect. Dis. 61, 892–899 (2015).

    • Google Scholar
  • 70.

    Singh, A., Lekshmi, M., Prakasan, S., Nayak, B. & Kumar, S. Multiple antibiotic-resistant, extended spectrum-β-lactamase (ESBL)-producing Enterobacteria in fresh seafood. Microorganisms 5, E53 (2017).

    • Google Scholar
  • 71.

    Zekar, F. M. et al. From farms to markets: Gram-negative bacteria resistant to third-generation cephalosporins in fruits and vegetables in a region of North Africa. Front. Microbiol. 8, 1569 (2017).

    • Google Scholar
  • 72.

    Yaici, L. et al. Spread of ESBL/AmpC-producing Escherichia coli and Klebsiella pneumoniae in the community through ready-to-eat sandwiches in Algeria. Int. J. Food Microbiol. 245, 66–72 (2017).

    • Google Scholar
  • 73.

    Projahn, M. et al. Contamination of chicken meat with extended-spectrum β-lactamase-producing Klebsiella pneumoniae and Escherichia coli during scalding and defeathering of broiler carcasses. Food Microbiol. 77, 185–191 (2019).

    • Google Scholar
  • 74.

    Rodrigues, C. et al. Description of Klebsiella africanensis sp. nov., Klebsiella variicola subsp. tropicalensis subsp. nov. and Klebsiella variicola subsp. variicola subsp. nov. Res. Microbiol. 170, 165–170 (2019).

    • Google Scholar
  • 75.

    Ford, P. & Avison, M. Evolutionary mapping of the SHV β-lactamase and evidence for two separate IS26-dependent bla SHV mobilization events from the Klebsiella pneumoniae chromosome. J. Antimicrob. Chemother. 54, 69–75 (2004).

    • Google Scholar
  • 76.

    Liakopoulos, A., Mevius, D. & Ceccarelli, D. A review of SHV extended-spectrum β-lactamases: neglected yet ubiquitous. Front. Microbiol. 5, 1374 (2016).

    • Google Scholar
  • 77.

    Turner, M. et al. Plasmid-borne bla SHV genes in Klebsiella pneumoniae are associated with strong promoters. J. Antimicrob. Chemother. 64, 960–964 (2009).

    • Google Scholar
  • 78.

    Ito, R. et al. Widespread fosfomycin resistance in Gram-negative bacteria attributable to the chromosomal fosA gene. mBio 8, e00749–e00817 (2017).

    • Google Scholar
  • 79.

    Li, J. et al. The nature and epidemiology of OqxAB, a multidrug efflux pump. Antimicrob. Resist. Infect. Control. 8, 44 (2019).

    • Google Scholar
  • 80.

    Bernardini, A. et al. The intrinsic resistome of Klebsiella pneumoniae. Int. J. Antimicrob. Agents. 53, 29–33 (2019).

    • Google Scholar
  • 81.

    Jana, B. et al. The secondary resistome of multidrug-resistant Klebsiella pneumoniae. Sci. Rep. 7, 42483 (2017).

    • Google Scholar
  • 82.

    Nicolas-Chanoine, M.-H., Mayer, N., Guyot, K., Dumont, E. & Pagès, J.-M. Interplay between membrane permeability and enzymatic barrier leads to antibiotic-dependent resistance in Klebsiella pneumoniae. Front. Microbiol. 9, 1422 (2018).

    • Google Scholar
  • 83.

    Xu, Q. et al. Efflux pumps AcrAB and OqxAB contribute to nitrofurantoin resistance in an uropathogenic Klebsiella pneumoniae isolate. Int. J. Antimicrob. Agents 54, 223–227 (2019).

    • Google Scholar
  • 84.

    He, F. et al. Tigecycline susceptibility and the role of efflux pumps in tigecycline resistance in KPC-producing Klebsiella pneumoniae. PLoS one 10, e0119064 (2015).

    • Google Scholar
  • 85.

    Fajardo-Lubián, A., Ben Zakour, N. L., Agyekum, A., Qi, Q. & Iredell, J. R. Host adaptation and convergent evolution increases antibiotic resistance without loss of virulence in a major human pathogen. PLoS Pathog. 15, e1007218 (2019). This study shows that deletions or mutations within OmpK35/36 porins are widespread and have emerged in multiple independent lineages of K. pneumoniae, facilitating enhanced resistance to β-lactams (including carbapenems) without significantly reducing the ability to colonize the gut or to cause pneumonia (in murine models).

    • Google Scholar
  • 86.

    Wong, J. L. C. et al. OmpK36-mediated carbapenem resistance attenuates ST258 Klebsiella pneumoniae in vivo. Nat. Commun. 10, 3957 (2019). This study experimentally confirms predictions that specific di-amino acid insertions in OmpK36 constrict its central pore, restricting diffusion of nutrients and carbapenems, and demonstrates using competition assays that these mutations do reduce fitness in the context of the murine pneumonia model.

    • Google Scholar
  • 87.

    Lunha, K. et al. High-level carbapenem-resistant OXA-48-producing Klebsiella pneumoniae with a novel OmpK36 variant and low-level, carbapenem-resistant, non-porin-deficient, OXA-181-producing Escherichia coli from Thailand. Diagn. Microbiol. Infect. Dis. 85, 221–226 (2016).

    • Google Scholar
  • 88.

    Cain, A. K. et al. Morphological, genomic and transcriptomic responses of Klebsiella pneumoniae to the last-line antibiotic colistin. Sci. Rep. 8, 9868 (2018).

    • Google Scholar
  • 89.

    Chang, H.-H. et al. Origin and proliferation of multiple-drug resistance in bacterial pathogens. Microbiol. Mol. Biol. Rev. 79, 101–116 (2015).

    • Google Scholar
  • 90.

    Lehtinen, S. et al. Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage. Proc. Natl Acad. Sci. USA 114, 1075–1080 (2017).

    • Google Scholar
  • 91.

    Conlan, S. et al. Single-molecule sequencing to track plasmid diversity of hospital-associated carbapenemase-producing Enterobacteriaceae. Sci. Transl Med. 6, 254ra126 (2014).

    • Google Scholar
  • 92.

    Martin, J. et al. Covert dissemination of carbapenemase-producing Klebsiella pneumoniae (KPC) in a successfully controlled outbreak: long- and short-read whole-genome sequencing demonstrate multiple genetic modes of transmission. J. Antimicrob. Chemother. 72, 3025–3034 (2017).

    • Google Scholar
  • 93.

    Sheppard, A. E. et al. Nested Russian doll-like genetic mobility drives rapid dissemination of the carbapenem resistance gene bla KPC. Antimicrob. Agents Chemother. 60, 3767–3778 (2016). This study, using a genomic comparison of carbapenem-resistant Enterobacteriaceae isolated from a single health-care institution, highlights the importance of strain, plasmid and transposon transmission for the dissemination of bla KPCcarbapenemase genes.

    • Google Scholar
  • 94.

    Buckner, M. M. C. et al. Clinically relevant plasmid–host interactions indicate that transcriptional and not genomic modifications ameliorate fitness costs of Klebsiella pneumoniae carbapenemase-carrying plasmids. mBio 9, e02303–e02317 (2018). This study demonstrates that the pKpQIL plasmid of ST258 alters K. pneumoniae gene expression and shows differences in transfer efficiencies of pKpQIL and related plasmids depending on the genetic background of donor and recipient strains.

    • Google Scholar
  • 95.

    Hardiman, C. et al. Horizontal transfer of carbapenemase-encoding plasmids and comparison with hospital epidemiological data. Antimicrob. Agents Chemother. 60, 4910–4919 (2016).

    • Google Scholar
  • 96.

    Lepuschitz, S. et al. Whole genome sequencing reveals resemblance between ESBL-producing and carbapenem resistant Klebsiella pneumoniae isolates from Austrian rivers and clinical isolates from hospitals. Sci. Total. Environ. 662, 227–235 (2019).

    • Google Scholar
  • 97.

    Paczosa, M. K. & Mecsas, J. Klebsiella pneumoniae: going on the offense with a strong defense. Microbiol. Mol. Biol. Rev. 80, 629–661 (2016).

    • Google Scholar
  • 98.

    Bengoechea, J. A. & Sa Pessoa, J. Klebsiella pneumoniae infection biology: living to counteract host defences. FEMS Microbiol. Rev. 43, 123–144 (2019).

    • Google Scholar
  • 99.

    Follador, R. et al. The diversity of Klebsiella pneumoniae surface polysaccharides. Microb. Genom. 2, e000073 (2016).

    • Google Scholar
  • 100.

    Wyres, K. L. et al. Identification of Klebsiella capsule synthesis loci from whole genome data. Microb. Genom. 2, e000102 (2016).

    • Google Scholar
  • 101.

    Bachman, M. A., Lenio, S., Schmidt, L., Oyler, J. E. & Weiser, J. N. Interaction of lipocalin 2, transferrin, and siderophores determines the replicative niche of Klebsiella pneumoniae during pneumonia. mBio 3, e00224-11 (2012).

    • Google Scholar
  • 102.

    Pan, Y.-J. et al. Genetic analysis of capsular polysaccharide synthesis gene clusters in 79 capsular types of Klebsiella spp. Sci. Rep. 5, 15573 (2015).

    • Google Scholar
  • 103.

    Whitfield, C. Biosynthesis and assembly of capsular polysaccharides in Escherichia coli. Annu. Rev. Biochem. 75, 39–68 (2006).

    • Google Scholar
  • 104.

    Ørskov, I. D. A. & Fife-Asbury, M. A. New Klebsiella capsular antigen, K82, and the deletion of five of those previously assigned. Int. J. Syst. Bacteriol. 27, 386–387 (1977).

    • Google Scholar
  • 105.

    Wick, R. R., Heinz, E., Holt, K. E. & Wyres, K. L. Kaptive Web: user-friendly capsule and lipopolysaccharide serotype prediction for Klebsiella genomes. J. Clin. Microbiol. 56, e00197–e00218 (2018).

    • Google Scholar
  • 106.

    Clarke, B. R. et al. Molecular basis for the structural diversity in serogroup O2-antigen polysaccharides in Klebsiella pneumoniae. J. Biol. Chem. 293, 4666–4679 (2018).

    • Google Scholar
  • 107.

    Guachalla, L. M. et al. Discovery of monoclonal antibodies cross-reactive to novel subserotypes of K. pneumoniae O3. Sci. Rep. 7, 6635 (2017).

    • Google Scholar
  • 108.

    Mostowy, R. J. & Holt, K. E. Diversity-generating machines: genetics of bacterial sugar-coating. Trends Microbiol. 26, 1008–1021 (2018).

    • Google Scholar
  • 109.

    Khater, F. et al. In silico analysis of usher encoding genes in Klebsiella pneumoniae and characterization of their role in adhesion and colonization. PLoS One 10, e0116215 (2015).

    • Google Scholar
  • 110.

    Murphy, C. N., Mortensen, M. S., Krogfelt, K. A. & Clegg, S. Role of Klebsiella pneumoniae type 1 and type 3 fimbriae in colonizing silicone tubes implanted into the bladders of mice as a model of catheter-associated urinary tract infections. Infect. Immun. 81, 3009–3017 (2013).

    • Google Scholar
  • 111.

    Bachman, M. A. et al. Klebsiella pneumoniae yersiniabactin promotes respiratory tract infection through evasion of lipocalin 2. Infect. Immun. 79, 3309–3316 (2011).

    • Google Scholar
  • 112.

    Russo, T. A., Olson, R., Macdonald, U., Beanan, J. & Davidson, B. A. Aerobactin, but not yersiniabactin, salmochelin, or enterobactin, enables the growth/survival of hypervirulent (hypermucoviscous) Klebsiella pneumoniae ex vivo and in vivo. Infect. Immun. 83, 3325–3333 (2015).

    • Google Scholar
  • 113.

    Russo, T. A. et al. Aerobactin mediates virulence and accounts for increased siderophore production under iron-limiting conditions by hypervirulent (hypermucoviscous) Klebsiella pneumoniae. Infect. Immun. 82, 2356–2367 (2014).

    • Google Scholar
  • 114.

    Fischbach, M. A. et al. The pathogen-associated iroA gene cluster mediates bacterial evasion of lipocalin 2. Proc. Natl Acad. Sci. USA 103, 16502–16507 (2006).

    • Google Scholar
  • 115.

    Lam, M. M. C. et al. Genetic diversity, mobilisation and spread of the yersiniabactin-encoding mobile element ICE Kp in Klebsiella pneumoniae populations. Microb. Genom. https://doi.org/10.1099/mgen.0.000196 (2018).

    • Google Scholar
  • 116.

    Lam, M. C. C. et al. Tracking key virulence loci encoding aerobactin and salmochelin siderophore synthesis in Klebsiella pneumoniae. Genome Med. 10, 77 (2018).

    • Google Scholar
  • 117.

    Holden, V. I., Bachman, M. A. & Holden, V. I. Diverging roles of bacterial siderophores during infection. Metallomics 7, 986–995 (2015).

    • Google Scholar
  • 118.

    Saha, P. et al. The bacterial siderophore enterobactin confers survival advantage to Salmonella in macrophages. Gut Microbes 10, 412–423 (2019).

    • Google Scholar
  • 119.

    Achard, M. E. S. et al. An antioxidant role for catecholate siderophores in Salmonella. Biochem. J. 454, 543–549 (2013).

    • Google Scholar
  • 120.

    Holden, V. I., Breen, P., Houle, S., Dozois, C. M. & Bachman, M. A. Klebsiella pneumoniae siderophores induce inflammation, bacterial dissemination, and HIF-1α stablization during pneumonia. mBio 7, e01397–e01416 (2016).

    • Google Scholar
  • 121.

    Lin, T.-L., Lee, C.-Z., Hsieh, P.-F., Tsai, S.-F. & Wang, J.-T. Characterization of integrative and conjugative element ICEKp1-associated genomic heterogeneity in a Klebsiella pneumoniae strain isolated from a primary liver abscess. J. Bacteriol. 190, 515–526 (2008).

    • Google Scholar
  • 122.

    Nassif, X., Fournier, J., Arondel, J. & Sansonetti, P. J. Mucoid phenotype of Klebsiella pneumoniae is a plasmid-encoded virulence factor. Infect. Immun. 57, 546–552 (1989).

    • Google Scholar
  • 123.

    Yang, X., Wai-Chi Chan, E., Zhang, R. & Chen, S. A conjugative plasmid that augments virulence in Klebsiella pneumoniae. Nat. Microbiol. 4, 2039–2043 (2019).

    • Google Scholar
  • 124.

    Nougayrède, J. P. et al. Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science 313, 848–851 (2006).

    • Google Scholar
  • 125.

    Lai, Y. C. et al. Genotoxic Klebsiella pneumoniae in Taiwan. PLoS One 9, e96292 (2014).

    • Google Scholar
  • 126.

    Lu, M.-C. et al. Colibactin contributes to the hypervirulence of pks + K1 CC23 Klebsiella pneumoniae in mouse meningitis infections. Front. Cell. Infect. Microbiol. 7, 1–14 (2017).

    • Google Scholar
  • 127.

    Wacharotayankun, R. et al. Enhancement of extracapsular polysaccharide synthesis in Klebsiella pneumoniae by RmpA2, which shows homology to NtrC and FixJ. Infect. Immun. 61, 3164–3174 (1993).

    • Google Scholar
  • 128.

    Arakawa, Y. et al. Biosynthesis of Klebsiella K2 capsular polysaccharide in Escherichia coli HB101 requires the functions of rmpA and the chromosomal cps gene cluster of the virulent strain Klebsiella pneumoniae Chedid (O1:K2). Infect. Immun. 59, 2043–2050 (1991).

    • Google Scholar
  • 129.

    Walker, K. A. et al. A Klebsiella pneumoniae regulatory mutant has reduced capsule expression but retains hypermucoviscosity. mBio 10, e00089–e00119 (2019). This study teases apart the roles of rmpA and a newly identified gene immediately downstream of it (rmpC) in hypermucoidy and capsule production.

    • Google Scholar
  • 130.

    Wu, C. C., Huang, Y. J., Fung, C. P. & Peng, H. L. Regulation of the Klebsiella pneumoniae Kpc fimbriae by the site-specific recombinase KpcI. Microbiology 156, 1983–1992 (2010).

    • Google Scholar
  • 131.

    Earle, S. G. et al. Identifying lineage effects when controlling for population structure improves power in bacterial association studies. Nat. Microbiol. 1, 16041 (2016).

    • Google Scholar
  • 132.

    Martin, R. M. et al. Identification of pathogenicity-associated loci in Klebsiella pneumoniae from hospitalized patients. mSystems 3, e00015–e00018 (2018). This genome-wide association study tests for K. pneumoniae genes associated with clinical isolates (bacteraemia or pneumonia) versus asymptomatic gut-colonizing isolates and demonstrates independent effects of the tellurite resistance operon ter and a psicose utilization locus.

    • Google Scholar
  • 133.

    Russo, T. A. et al. Identification of biomarkers for differentiation of hypervirulent Klebsiella pneumoniae from classical K. pneumoniae. J. Clin. Microbiol. 56, e00776-18 (2018). This study is the first systematic exploration of virulence markers and their relative effect on prediction of the hypervirulence phenotype, highlighting the importance of the aerobactin synthesis locus iuc and other plasmid co-located loci.

    • Google Scholar
  • 134.

    Liu, C. & Guo, J. Hypervirulent Klebsiella pneumoniae (hypermucoviscous and aerobactin positive) infection over 6 years in the elderly in China: antimicrobial resistance patterns, molecular epidemiology and risk factor. Ann. Clin. Microbiol. Antimicrob. 18, 4 (2019).

    • Google Scholar
  • 135.

    Ye, M. et al. Clinical and genomic analysis of liver abscess-causing Klebsiella pneumoniae identifies new liver abscess-associated virulence genes. Front. Cell Infect. Microbiol. 6, 1–12 (2016).

    • Google Scholar
  • 136.

    Wu, K. M. et al. Genome sequencing and comparative analysis of Klebsiella pneumoniae NTUH-K2044, a strain causing liver abscess and meningitis. J. Bacteriol. 191, 4492–4501 (2009).

    • Google Scholar
  • 137.

    Chen, Y., Chang, H., Lai, Y., Pan, C. & Tsai, S. Sequencing and analysis of the large virulence plasmid pLVPK of Klebsiella pneumoniae CG43. Gene 337, 189–198 (2004).

    • Google Scholar
  • 138.

    Lery, L. M. et al. Comparative analysis of Klebsiella pneumoniae genomes identifies a phospholipase D family protein as a novel virulence factor. BMC Biol. 12, 41 (2014).

    • Google Scholar
  • 139.

    Tu, Y. C. et al. Genetic requirements for Klebsiella pneumoniae-induced liver abscess in an oral infection model. Infect. Immun. 77, 2657–2671 (2009).

    • Google Scholar
  • 140.

    Bulger, J., MacDonald, U., Olson, R., Beanan, J. & Russo, T. A. Metabolite transporter PEG344 is required for full virulence of hypervirulent Klebsiella pneumoniae strain hvKP1 after pulmonary but not subcutaneous challenge. Infect. Immun. 85, e00093-17 (2017).

    • Google Scholar
  • 141.

    Xie, Y. et al. Emergence of the third-generation cephalosporin-resistant hypervirulent Klebsiella pneumoniae due to the acquisition of a self-transferable bla DHA-1-carrying plasmid by an ST23 strain. Virulence 9, 838–844 (2018).

    • Google Scholar
  • 142.

    Surgers, L., Boyd, A., Girard, P. M., Arlet, G. & Decré, D. ESBL-producing strain of hypervirulent Klebsiella pneumoniae K2, France. Emerg. Infect. Dis. 22, 1687–1688 (2016).

    • Google Scholar
  • 143.

    Shen, D. et al. Emergence of a multidrug-resistant hypervirulent Klebsiella pneumoniae of ST23 with a rare bla CTX-M-24-harboring virulence plasmid. Antimicrob. Agents Chemother. 63, e02273–e02318 (2019).

    • Google Scholar
  • 144.

    Dong, N., Lin, D., Zhang, R., Chan, E. W. C. & Chen, S. Carriage of bla KPC-2 by a virulence plasmid in hypervirulent Klebsiella pneumoniae. J. Antimicrob. Chemother. 73, 3317–3321 (2018).

    • Google Scholar
  • 145.

    Dong, N. et al. Genome analysis of clinical multilocus sequence Type 11 Klebsiella pneumoniae from China. Microb. Genomics 4, https://doi.org/10.1099/mgen.0.000149 (2018).

  • 146.

    Weingarten, R. A. et al. Genomic analysis of hospital plumbing reveals diverse reservoir of bacterial plasmids conferring carbapenem resistance. mBio 9, e02011–e02017 (2018).

    • Google Scholar
  • 147.

    Sherry, N. L. et al. Genomics for molecular epidemiology and detecting transmission of carbapenemase-producing Enterobacterales in Victoria, Australia, 2012–2016. J. Clin. Microbiol. 57, e00573-19 (2019).

    • Google Scholar
  • 148.

    Brisse, S. & Verhoef, J. Phylogenetic diversity of Klebsiella pneumoniae and Klebsiella oxytoca clinical isolates revealed by randomly amplified polymorphic DNA, gyrA and parC genes sequencing and automated ribotyping. Int. J. Syst. Evol. Microbiol. 51, 915–924 (2001).

    • Google Scholar
  • 149.

    Brisse, S., Passet, V. & Grimont, P. A. D. Description of Klebsiella quasipneumoniae sp., isolated from human infections, with two subspecies, Klebsiella quasipneumoniae subsp. quasipneumoniae subsp. nov. and Klebsiella quasipneumoniae subsp. similipneumoniae subsp. nov., and. demonstration that Klebsiella singaporensis is a junior heterotypic synonym of Klebsiella variicola. Int. J. Syst. Evol. Microbiol. 64, 3146–3152 (2014).

    • Google Scholar
  • 150.

    Rosenblueth, M., Martínez, L., Silva, J. & Martínez-Romero, E. Klebsiella variicola, a novel species with clinical and plant-associated isolates. Syst. Appl. Microbiol. 27, 27–35 (2004).

    • Google Scholar
  • 151.

    Long, S. W. et al. Whole-genome sequencing of a human clinical isolate of the novel species Klebsiella quasivariicola sp. nov. Genome Announc. 5, e01057-17 (2017).

    • Google Scholar
  • 152.

    Blin, C., Passet, V., Touchon, M., Rocha, E. P. C. & Brisse, S. Metabolic diversity of the emerging pathogenic lineages of Klebsiella pneumoniae. Env. Microbiol. 19, 1881–1898 (2017). This study is the first exploration of metabolic variation among diverse K. pneumoniae lineages and other members of the species complex, showing that metabolic capabilities — in particular, carbon substrate utilization — can vary substantially between strains.

    • Google Scholar
  • 153.

    Potter, R. F. et al. Population structure, antibiotic resistance, and uropathogenicity of Klebsiella variicola. mBio 9, e02481-18 (2018).

    • Google Scholar
  • 154.

    Mathers, A. J. et al. Klebsiella quasipneumoniae provides a window into carbapenemase gene transfer, plasmid rearrangements, and patient interactions with the hospital environment. Antimicrob. Agents Chemother. 63, e02513–e02518 (2019).

    • Google Scholar
  • 155.

    Brinkac, L. M. et al. Emergence of New Delhi metallo-β-lactamase (NDM-5) in Klebsiella quasipneumoniae from neonates in a Nigerian hospital. mSphere 4, e00685-18 (2019).

    • Google Scholar
  • 156.

    Rodríguez-Medina, N., Barrios-Camacho, H., Duran-Bedolla, J. & Garza-Ramos, U. Klebsiella variicola: an emerging pathogen in humans. Emerg. Microbes Infect. 8, 973–988 (2019).

    • Google Scholar
  • 157.

    Breurec, S. et al. Liver abscess caused by infection with community-acquired Klebsiella quasipneumoniae subsp. quasipneumoniae. Emerg. Infect. Dis. 22, 529–531 (2016).

    • Google Scholar
  • 158.

    Brisse, S. & Van Duijkeren, E. Identification and antimicrobial susceptibility of 100 Klebsiella animal clinical isolates. Vet. Mirobiol. 105, 307–312 (2005).

    • Google Scholar
  • 159.

    Martínez-Romero, E. et al. Genome misclassification of Klebsiella variicola and Klebsiella quasipneumoniae isolated from plants, animals and humans. Salud Publica. Mex. 60, 52–62 (2018).

    • Google Scholar
  • 160.

    Ramirez, M. S., Iriarte, A., Reyes-Lamothe, R., Sherratt, D. J. & Tolmasky, M. E. Small Klebsiella pneumoniae plasmids: neglected contributors to antibiotic resistance. Front. Microbiol. 10, 2182 (2019).

    • Google Scholar
  • 161.

    Carattoli, A. et al. In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrob. Agents Chemother. 58, 3895–3903 (2014).

    • Google Scholar
  • 162.

    Robertson, J. & Nash, J. H. E. MOB-suite: software tools for clustering, reconstruction and typing of plasmids from draft assemblies. Microb. Genom. 4, https://doi.org/10.1099/mgen.0.000206 (2018).

  • 163.

    Orlek, A. et al. Ordering the mob: insights into replicon and MOB typing schemes from analysis of a curated dataset of publicly available plasmids. Plasmid 91, 42–52 (2017).

    • Google Scholar
  • 164.

    Arredondo-Alonso, S., Willems, R. J., van Schaik, W. & Schürch, A. C. On the (im)possibility of reconstructing plasmids from whole-genome short-read sequencing data. Microb. Genom. 3, e000128 (2017).

    • Google Scholar
  • 165.

    De Maio, N. et al. Comparison of long-read sequencing technologies in the hybrid assembly of complex bacterial genomes. Microb. Genom. https://doi.org/10.1099/mgen.0.000294 (2019).

  • 166.

    Villa, L. et al. Diversity, virulence and antimicrobial resistance of the KPC-producing Klebsiella pneumoniae ST307 clone. Microb. Genom. https://doi.org/10.1099/mgen.0.000110 (2017).

  • 167.

    Yeh, K.-M. et al. Revisiting the importance of virulence determinant magA and its surrounding genes in Klebsiella pneumoniae causing pyogenic liver abscesses: exact role in serotype K1 capsule formation. J. Infect. Dis. 201, 1259–1267 (2010).

    • Google Scholar
  • 168.

    Yu, W.-L., Lee, M.-F., Tang, H.-J., Chang, M.-C. & Chuang, Y.-C. Low prevalence of rmpA and high tendency of rmpA mutation correspond to low virulence of extended spectrum β-lactamase-producing Klebsiella pneumoniae isolates. Virulence 6, 162–172 (2015).

    • Google Scholar
  • 169.

    Martinez, J., Martinez, L., Rosenblueth, M., Silva, J. & Martinez-Romero, E. How are gene sequence analyses modifying bacterial taxonomy? The case of Klebsiella. Int. Microbiol. 7, 261–268 (2004).

    • Google Scholar
  • 170.

    Ejaz, H. et al. Phylogenetic analysis of Klebsiella pneumoniae from hospitalized children, Pakistan. Emerg. Infect. Dis. 23, 1872–1875 (2017).

    • Google Scholar
  • 171.

    Cerqueira, G. C. et al. Multi-institute analysis of carbapenem resistance reveals remarkable diversity, unexplained mechanisms, and limited clonal outbreaks. Proc. Natl Acad. Sci. USA 114, 1135–1140 (2017).

    • Google Scholar
  • 172.

    Moradigaravand, D., Martin, V., Peacock, S. J. & Parkhill, J. Evolution and epidemiology of multidrug-resistant Klebsiella pneumoniae in the United Kingdom. mBio 8, e01976-16 (2017).

    • Google Scholar
  • 173.

    Liu, L. et al. Carbapenem-resistant isolates of the Klebsiella pneumoniae complex in western China: the common ST11 and the surprising hospital-specific types. Clin. Infect. Dis. 67 S263–S265 (2018).

    • Google Scholar
  • 174.

    Ocampo, A. M. et al. A two-year surveillance in five Colombian tertiary care hospitals reveals high frequency of non-CG258 clones of carbapenem-resistant Klebsiella pneumoniae with distinct clinical characteristics. Antimicrob. Agents Chemother. 60, 332–342 (2015).

    • Google Scholar
  • 175.

    Andrade, L. N. et al. Virulence genes, capsular and plasmid types of multidrug-resistant CTX-M(-2, -8, -15) and KPC-2-producing Klebsiella pneumoniae isolates from four major hospitals in Brazil. Diagn. Microbiol. Infect. Dis. 91, 164–168 (2018).

    • Google Scholar
  • 176.

    Deleo, F. R. et al. Molecular dissection of the evolution of carbapenem-resistant multilocus sequence type 258 Klebsiella pneumoniae. Proc. Natl Acad. Sci. USA 111, 4988–4993 (2014).

    • Google Scholar
  • 177.

    Lowe, M. et al. Klebsiella pneumoniae ST307 with bla OXA-181, South Africa, 2014–2016. Emerg. Infect. Dis. 25, 739–747 (2019).

    • Google Scholar
  • 178.

    Chung The, H. et al. A high-resolution genomic analysis of multidrug-resistant hospital outbreaks of Klebsiella pneumoniae. EMBO Mol. Med. 7, 227–239 (2015).

    • Google Scholar

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