Interplay between resistance and virulence markers in Enterobacteriales carbapenemase producers

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First outbreak of NDM-1-producing Klebsiella pneumoniae ST11 in a Portuguese hospital centre during the COVID-19 pandemic

Publication . Mendes, Gabriel; Ramalho, João Francisco; Duarte, Aida; Pedrosa, Adriana; Silva, Ana Cristina; Méndez, Lucía; Caneiras, Catia

New Delhi metallo-β-lactamase (NDM) carbapenemase has been considered a global threat due to its worldwide widespread in recent years. In Portugal, a very low number of infections with NDM-producing Enterobacterales has been reported. A total of 52 strains from 40 patients and 1 environmental sample isolated during COVID-19 pandemic were included in this study. Wholegenome sequencing (WGS) was performed on 20 carbapenemase-producing strains, including 17 NDM-1-producing Klebsiella pneumoniae ST11-KL105 lineage strains, one NDM-1-producing Escherichia coli ST58 strain and one KPC-3-producing K. pneumoniae ST147 strain, recovered from a total of 19 patients. Of interest, also one NDM-1-producing K. pneumoniae ST11-KL105 was collected from the hospital environment. Genome-wide phylogenetic analysis revealed an ongoing dissemination of NDM-1-producing K. pneumoniae ST11 strains (n = 18) with the same genetic features seen across multiple wards. Furthermore, the ST58 E. coli strain, collected from a patient rectal swab that was also colonised with a K. pneumoniae strain, also showed the IncFIA plasmid replicon and the blaNDM-1 gene (preceded by IS30 and followed by genes bleMBL, trpF, dsbC, cutA, groES and groEL). The blaNDM-1 is part of Tn125-like identical to those reported in Poland, Italy and India. The blaKPC-3 K. pneumoniae ST147-KL64 strain has the genetic environment Tn4401d isoform. In conclusion, herein we report the molecular epidemiology, resistome, virulome and mobilome of the first NDM-1 carbapenemase outbreak caused by K. pneumoniae ST11-KL105 lineage during the COVID-19 pandemic in Portugal. Moreover, the outbreak strains characterised included seventeen different patients (infected and colonised) and one environmental sample which also emphasises the role of commensal and hospital environment strains in the dissemination of the outbreak.

2022Journal article

Open access

Virulence factors in carbapenem-resistant hypervirulent Klebsiella pneumoniae

Publication . Mendes, Gabriel; Santos, Maria Leonor; Ramalho, João Francisco; Duarte, Aida; Caneiras, Catia

Hypervirulence and carbapenem-resistant have emerged as two distinct evolutionary pathotypes of Klebsiella pneumoniae, with both reaching their epidemic success and posing a great threat to public health. However, as the boundaries separating these two pathotypes fade, we assist a worrisome convergence in certain high-risk clones, causing hospital outbreaks and challenging every therapeutic option available. To better understand the basic biology of these pathogens, this review aimed to describe the virulence factors and their distribution worldwide among carbapenem-resistant highly virulent or hypervirulent K. pneumoniae strains, as well as to understand the interplay of these virulence strains with the carbapenemase produced and the sequence type of such strains. As we witness a shift in healthcare settings where carbapenemresistant highly virulent or hypervirulent K. pneumoniae are beginning to emerge and replace classical K. pneumoniae strains, a better understanding of these strains is urgently needed for immediate and appropriate response.

2023Journal article

Open access

Genomic characterisation of a novel KPC-98-producing clinical Klebsiella pneumoniae strain conferring resistance to ceftazidime/avibactam

Publication . Mendes, Gabriel; Santos, Maria Leonor; Ramalho, João Francisco; Bruschy-Fonseca, Ana; Lito, Luís; Pedro, Diogo; Duarte, Aida; Cristino, José Melo; Caneiras, Catia

Ceftazidime/avibactam (CZA) is a novel drug that inactivates Ambler class A, including Klebsiella pneumoniae carbapenemases (KPC), class C and class D β-lactamases, but is not active against metallo-β-lactamases (class B). Despite its limited use worldwide, emerging cases of CZA-resistant isolates producing variants of the blaKPC gene have been reported. In this study, we report a novel KPC-98 variant conferring CZA resistance identified in a highly virulent and multidrug-resistant clinical isolate of K. pneumoniae, belonging to the high-risk international clone sequence type 13 (ST13).

2023Journal article

Restricted access

Whole-genome sequencing enables molecular characterization of non-clonal group 258 high-risk clones (ST13, ST17, ST147 and ST307) among Carbapenem-resistant Klebsiella pneumoniae from a tertiary university hospital centre in Portugal

Publication . Mendes, Gabriel; Ramalho, João Francisco; Bruschy Fonseca, Ana; Lito, Luís; Duarte, Aida; Cristino, José Melo; Caneiras, Catia

The carbapenem-resistant Enterobacterales (CRE) strains have been identified by the World Health Organization as critical priority pathogens in research and development of diagnostics, treatments, and vaccines. However, recent molecular information about carbapenem-resistant K. pneumoniae (CRK) epidemiology in Portugal is still scarce. Thus, this study aimed to provide the molecular epidemiology, resistome, and virulome of CRK clinical strains recovered from a tertiary care hospital centre (2019–2021) using polymerase chain reaction (PCR) and the advanced molecular technique whole-genome sequencing (WGS). PCR amplification of carbapenemase genes was performed in 437 carbapenem-resistant K. pneumoniae strains. The most frequent carbapenemases were: KPC-3 (42%), followed by OXA-181 (20%), GES-5 (0.2%), and NDM-1 (0.2%). Additionally, 10 strains (2%) coproduced KPC-3 and OXA-181, and 1 strain coproduced KPC-3 and OXA-48 (0.2%). The genomic population structure of 68 strains characterized by WGS demonstrated the ongoing dissemination of four main high-risk clones: ST13, ST17, ST147, and ST307, while no clones belonging to the European predominant clonal groups (CG15 and CG258) were found. Moreover, we describe one K. pneumoniae ST39-KL62 that coproduced the NDM-1 carbapenemase and the extended-spectrum beta-lactamase CTX-M-15, and one K. pneumoniae ST29-KL54 GES-5 and BEL-1 coproducer. Furthermore, a high prevalence of iron siderophores were present in all CRK strains, with several strains presenting both colibactin and the hypermucoviscosity phenotype. Thus, the data presented here highlight an uncommon molecular epidemiology pattern in Portugal when compared with most European countries, further supporting the emergence and dissemination of nonclonal group 258 hypervirulent multidrug high-risk clones and the need to promote in-depth hospital molecular surveillance studies.

2022Journal article

Open access