Genomic insights into the diversity, virulence and resistance of Klebsiella pneumoniae extensively drug resistant clinical isolates

Abstract

Klebsiella pneumoniae has been implicated in wide-ranging nosocomial outbreaks, causing severe infections without effective treatments due to antibiotic resistance. Here, we performed genome sequencing of 70 extensively drug resistant clinical isolates, collected from Brasília’s hospitals (Brazil) between 2010 and 2014. The majority of strains (60 out of 70) belonged to a single clonal complex (CC), CC258, which has become distributed worldwide in the last two decades. Of these CC258 strains, 44 strains were classified as sequence type 11 (ST11) and fell into two distinct clades, but no ST258 strains were found. These 70 strains had a pan-genome size of 10 366 genes, with a core-genome size of ~4476 genes found in 95 % of isolates. Analysis of sequences revealed diverse mechanisms of resistance, including production of multidrug efflux pumps, enzymes with the same target function but with reduced or no affinity to the drug, and proteins that protected the drug target or inactivated the drug. β-Lactamase production provided the most notable mechanism associated with K. pneumoniae . Each strain presented two or three different β-lactamase enzymes, including class A (SHV, CTX-M and KPC), class B and class C AmpC enzymes, although no class D β-lactamase was identified. Strains carrying the NDM enzyme involved three different ST types, suggesting that there was no common genetic origin.

Dissemination of a single ST11 clone of OXA-48-producing Klebsiella pneumoniae within a large polyclonal hospital outbreak determined by genomic sequencing

“…One of these was ST11, a lineage with worldwide distribution and known to cause hospital outbreaks of ESBL-and carbapenemase-producers. With such a broad distribution ST11 has a large and diverse population [5,31] yet the isolates from the same hospitals tend to be more related between them than to those of other sites [31] showing a pattern of local expansion. To understand the evolution of a large Kp-OXA hospital epidemic we have sequenced and analysed a collection of 97 ST11 Kp-OXA isolates obtained from two hospitals in Madrid during the early years of the outbreak.…”

The Spread of NDM-1 and NDM-7-Producing Klebsiella pneumoniae Is Driven by Multiclonal Expansion of High-Risk Clones in Healthcare Institutions in the State of Pará, Brazilian Amazon Region

“…ST1264 has emerged (and probably highly restricted) in China, causing bloodstream infection, and recently associated with ESBL-producing isolates [ 56 , 57 ]. Recently, several reports indicate ST340/CC258 has a critical role in expanding NDM-producing strains in Brazil, being associated with monoclonal outbreaks, colistin-resistant-isolates, and isolates co-harboring bla NDM and bla KPC genes [ 9 , 12 , 18 , 58 ]. Epidemic ST11 was the most prevalent in our study, found dispersed in five distinct hospitals in different periods, and interestingly present in pediatric settings at H3, co-harboring bla NDM, and bla KPC , indicating endemicity and spread these resistance markers in this environment.…”

“…However, it has demonstrated a concerning spread, with strains particularly harboring the bla NDM gene and rarely associated with bla KPC [ 54 , 61 ]. Since its first report in Brazil by Gonçalves et al [ 17 ], ST15/CC15 has been detected in clinical and environmental samples, but with few reported NDM-producing strains in Porto Alegre (South region), Rio de Janeiro (Southeast), and Brasilia (Midwest region) cities [ 9 , 50 , 54 , 62 ]. According to our data, NDM-producing ST15/CC15 strains have been found circulating in four different hospitals since 2018 and mostly present adult settings, suggesting an early and rapid spread across Brazil.…”

“…Carbapenem-resistant K. pneumoniae isolates (CR-Kp) are usually detected harboring the bla KPC gene, with endemicity reported in Brazil and several other countries, while the dissemination of NDM-producing K. pneumoniae has increased in several regions, and mainly during the COVID-19 pandemic [ 3 , 4 , 5 , 6 , 7 , 8 ]. Such highly resistant-strains carrying resistance mechanisms are associated with so-called high-risk clones (HRCs), particularly to strains belonging to the clonal complex 258 (CC258) and CC15, which have been detected in multiclonal expansion at several Brazilian hospitals [ 9 , 10 , 11 , 12 , 13 , 14 ].…”

Estudo da colonização intestinal como fator de risco para infecção e disseminação de enterobactérias resistentes aos carbapenêmicos no ambiente hospitalar

“…(250,252) Esse aumento de KpRC no HIAE e em outros centros de São Paulo seguem o mesmo cenário observado em outros países a partir de 2010, correlacionando o aumento da resistência à disseminação de genes de resistência adquiridos, sendo que em 2019 e 2020 os números de genes de resistência adquiridos aumentaram significativamente no mundo, semelhante ao encontrado também para ERC no HIAE em 2019 e 2020. (8) Nos períodos onde foi observado maior incidência de ERC no HIAE (207,208,253) Interessantemente, cepas ST11 também se tornaram a população predominante de Klebsiella pneumoniae em um hospital localizado na Espanha, onde foi observada a substituição de Klebsiella pneumoniae ST405 por ST11 a partir de 2014. (254) principamente um ou outro arsenal, principalmente.…”