Genomic characterization of a local epidemic Pseudomonas aeruginosa reveals specific features of the widespread clone ST395

Abstract

Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen with several clones being frequently associated with outbreaks in hospital settings. ST395 is among these so-called ‘international’ clones. We aimed here to define the biological features that could have helped the implantation and spread of the clone ST395 in hospital settings. The complete genome of a multidrug resistant index isolate (DHS01) of a large hospital outbreak was analysed. We identified DHS01-specific genetic elements, among which were identified those shared with a panel of six independent ST395 isolates responsible for outbreaks in other hospitals. DHS01 has the fifth largest chromosome of the species (7.1 Mbp), with most of its 1555 accessory genes borne by either genomic islands (GIs, n=48) or integrative and conjugative elements (ICEs, n=5). DHS01 is multidrug resistant mostly due to chromosomal mutations. It displayed signatures of adaptation to chronic infection in part due to the loss of a 131 kbp chromosomal fragment. Four GIs were specific to the clone ST395 and contained genes involved in metabolism (GI-4), in virulence (GI-6) and in resistance to copper (GI-7). GI-7 harboured an array of six copper transporters and was shared with non-pathogenic Pseudomonas sp. retrieved from copper-contaminated environments. Copper resistance was confirmed phenotypically in all other ST395 isolates and possibly accounted for the spreading capability of the clone in hospital outbreaks, where water networks have been incriminated. This suggests that genes transferred from copper-polluted environments may have favoured the implantation and spread of the international clone P. aeruginosa ST395 in hospital settings.

From Pan-genome to the Genomic Context of the Two Integrons of ST-111 Pseudomonas Aeruginosa AG1: A VIM-2-carrying Old-acquaintance and a Novel Imp-18-carrying Integron

“…2 and 3), including the genomic islands clusters harboring the two integrons (GIC VIM−2 and GIC IMP−18 ). Genomic islands groups have been reported before as integrative and conjugative elements or ICEs (16), but ICEs in PaeAG1 (using ICEberg 2.0 platform, https://db-mml.sjtu.edu.cn/ICE nder/ICE nder.html) overlap with other GICs but none with GIC VIM−2 and GIC IMP−18 . Since size of the core-genome and its content is not well known (57), prediction methods are required to de ne accessory regions, but outcome depends on algorithms (56), which could explain differences and the GICs.…”

“…On the other hand, this prominent number of genomic islands in PaeAG1 and other ST-111 strains can be explained due to the absence of a functional CRISPR-Cas system (bacterial defense system against foreign DNA) and consequent high number of successful events of horizontal gene transfer (16). This genome plasticity of individual strains represents an advantage for P. aeruginosa to t the needs for survival in virtually any environment (50).…”

“…Jointly with ST-235 and ST-175 genotypes, ST-111 belong to the high-risk group in P. aeruginosa (8). High-risk clones are frequently associated with epidemics where multidrug resistance confounds treatment (16).…”

“…In this context, it is considered that P. aeruginosa high-risk clones are part of a non-clonal epidemic population structure (8,16), many carrying genomic determinants such as carbapenemases or extended-spectrum β-lactamases (8). Carbapenemases include Ambler class A enzymes such as KPC and GES variants, Ambler class B MBLs (IMP, VIM, SPM, GIM, NDM and FIM type), and Amber class D (OXA variants) enzymes (17,18).…”

“…Several studies at genomic level have been implemented to describe the molecular diversity in P. aeruginosa (including high-risk clones) using different comparative approaches (13,16,42).…”