Dissemination of metallo- -lactamase-producing Pseudomonas aeruginosa of sequence type 235 in Asian countries

k Carbapenems are a mainstay of treatment for infections caused by Pseudomonas aeruginosa. Carbapenem resistance mediated by metallo-␤-lactamases (MBLs) remains uncommon in the United States, despite the worldwide emergence of this group of enzymes. Between March 2012 and May 2013, we detected MBL-producing P. aeruginosa in a university-affiliated health care system in northeast Ohio. We examined the clinical characteristics and outcomes of patients, defined the resistance determinants and structure of the genetic element harboring the bla MBL gene through genome sequencing, and typed MBL-producing P. aeruginosa isolates using pulsed-field gel electrophoresis (PFGE), repetitive sequence-based PCR (rep-PCR), and multilocus sequence typing (MLST). Seven patients were affected that were hospitalized at three community hospitals, a long-term-care facility, and a tertiary care center; one of the patients died as a result of infection. Isolates belonged to sequence type 233 (ST233) and were extensively drug resistant (XDR), including resistance to all fluoroquinolones, aminoglycosides, and ␤-lactams; two isolates were nonsusceptible to colistin. The bla MBL gene was identified as bla VIM-2 contained within a class 1 integron (In559), similar to the cassette array previously detected in isolates from Norway, Russia, Taiwan, and Chicago, IL. Genomic sequencing and assembly revealed that In559 was part of a novel 35-kb region that also included a Tn501-like transposon and Salmonella genomic island 2 (SGI2)-homologous sequences. This analysis of XDR strains producing VIM-2 from northeast Ohio revealed a novel recombination event between Salmonella and P. aeruginosa, heralding a new antibiotic resistance threat in this region's health care system.

Section: Discussionmentioning

confidence: 75%

Extensively Drug-Resistant Pseudomonas aeruginosa Isolates Containing bla _VIM-2 and Elements of Salmonella Genomic Island 2: a New Genetic Resistance Determinant in Northeast Ohio

Pérez

Hujer

Marshall

et al. 2014

“…This observation indicates both the chromosomal and plasmid locations of bla VIM-2 . In addition to the identification of the integron structure in ST244 and ST640, this genetic structure has been identified in several other different genetic backgrounds of P. aeruginosa, such as ST233 (13,31), ST234 (27), ST235 (27,33), and ST1488 (10), with wide geographical distribution. This suggests that the integron is associated with mobile genetic structures facilitating horizontal transfer and dissemination, as previously suggested (29).…”

mentioning

confidence: 99%

Identification of VIM-2-Producing Pseudomonas aeruginosa from Tanzania Is Associated with Sequence Types 244 and 640 and the Location of bla _VIM-2 in a TniC Integron

Moyo

Haldorsen

Aboud

et al. 2015

e Epidemiological data on carbapenemase-producing Gram-negative bacteria on the African continent are limited. Here, we report the identification of VIM-2-producing Pseudomonas aeruginosa isolates in Tanzania. Eight out of 90 clinical isolates of P. aeruginosa from a tertiary care hospital in Dar es Salaam were shown to harbor bla VIM-2 . The bla VIM-2 -positive isolates belonged to two different sequence types (ST), ST244 and ST640, with bla VIM-2 located in an unusual integron structure lacking the 3= conserved region of qac⌬E1-sul1. Pseudomonas aeruginosa is an opportunistic pathogen associated with a number of nosocomial infections. Carbapenems (i.e., meropenem and imipenem) are often the treatment of choice for infections caused by P. aeruginosa that is resistant to other antipseudomonal ␤-lactams (1). However, the emergence and spread of acquired carbapenemases, particularly metallo-␤-lactamases (MBLs), among P. aeruginosa are threatening the usefulness of carbapenems (2). Resistance to carbapenems in P. aeruginosa can also occur due to impermeability, efflux mechanisms, and other ␤-lactamases, including overexpression of the chromosomal AmpC (3).Several acquired MBLs have been identified in P. aeruginosa, including the VIM, IMP, SPM, GIM, AIM, FIM, and NDM enzymes (2, 4). The genes encoding these MBLs are associated with mobile genetic elements, such as insertion sequence common region (ISCR) elements, transposons, and plasmids, and as gene cassettes in integron structures. The dissemination of the various MBLs among P. aeruginosa isolates has been shown to occur in many different genetic backgrounds (5). However, two major clonal complexes (CC), CC235 and CC111, predominate, particularly with respect to the dissemination of VIM enzymes (5).On the African continent, an increasing number of reports indicates that MBL-producing, and in particular VIM-2-producing, P. aeruginosa is widespread in Africa. VIM-2-producing P. aeruginosa isolates have been observed in Tunisia (6-8), Kenya (9), the Ivory Coast (10), Algeria (11), and South Africa (12). Further, reports have shown the import of P. aeruginosa with VIM-2 from African countries (Ghana, Tunisia, and Egypt) into Europe (13-15).(Part of this study was presented at the 22nd European Congress of Microbiology and Infectious Diseases, 31 March to 3 April 2012, London, United Kingdom.)The aim of this study was to determine the occurrence and molecular epidemiology of MBL-producing P. aeruginosa isolates identified from clinical specimens at a tertiary hospital in Dar es Salaam, Tanzania. This was a cross-sectional study conducted at the Central Pathology Laboratory, Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania. MNH is the largest tertiary health care facility in Tanzania and serves as a university teaching and referral hospital to the population of Dar es Salaam and the whole country. The study included 90 clinical isolates of P. aeruginosa consecutively collected from May 2010 to July 2011. Duplicate isolates were excluded from the study. Only i...

“…Among the several acquired MBLs reported in Gram-negative pathogens, the VIM-type enzymes have been detected worldwide in a large number of species, including Pseudomonas aeruginosa, other Gram-negative nonfermenters (GNNFs), and Enterobacteriaceae, and together with the IMP and NDM types, they are currently the MBLs with the greatest epidemiological and clinical impact (1)(2)(3). In P. aeruginosa, VIM-type enzymes are overall the most widespread and prevalent acquired MBLs (1,(4)(5)(6)(7).…”

mentioning

confidence: 99%

Tn 6249 , a New Tn 6162 Transposon Derivative Carrying a Double-Integron Platform and Involved with Acquisition of the bla _VIM-1 Metallo-β-Lactamase Gene in Pseudomonas aeruginosa

Pilato

Pollini

Rossolini

2015

cThe In70.2 integron platform appears to be a conserved structure involved in the dissemination of the bla VIM-1 metallo-␤-lactamase gene in Pseudomonas aeruginosa. The genetic context of the In70.2 integron platform from P. aeruginosa VR-143/97, the VIM-1-producing index strain isolated in Italy in 1997, was fully characterized by a next-generation sequencing approach refined by conventional sequencing. The In70.2 integron platform from VR-143/97 was found to be associated with a defective Tn402-like transposon inserted into the urf2 gene of a Tn3 family transposon of an original structure, named Tn6249, which also carried a partially deleted mer operon and an In90 integron platform in a tail-to-tail orientation. Tn6249 was inserted into a PACS171b-like genomic island, which was in turn inserted into the endA gene of the Pseudomonas chromosomal backbone. Tn6249 showed a similar structure and a conserved location with respect to that of Tn6060, a Tn3 family transposon associated with In70.2 and carrying a double-integron platform, which was detected in a VIM-1-producing P. aeruginosa strain isolated in Australia in 2008. Both Tn6249 and Tn6060 are apparently derived from Tn6162, a mercury resistance transposon carrying an integron platform, which was found in P. aeruginosa isolates from different geographic locations. The conservation of the genetic context of Tn6249 and Tn6060 suggests an in situ evolution of these elements after the insertion of a Tn6162-like ancestor into the PACS171b-like genomic island (GI) present in the genome of a successful widespread P. aeruginosa clonal lineage. Metallo-␤-lactamases (MBLs) have emerged as a major threat to antimicrobial chemotherapy due to their extended-spectrum activity against most ␤-lactams, including carbapenems, and their resistance to ␤-lactamase inhibitors, such as clavulanate, sulbactam, tazobactam, and avibactam (1). Among the several acquired MBLs reported in Gram-negative pathogens, the VIM-type enzymes have been detected worldwide in a large number of species, including Pseudomonas aeruginosa, other Gram-negative nonfermenters (GNNFs), and Enterobacteriaceae, and together with the IMP and NDM types, they are currently the MBLs with the greatest epidemiological and clinical impact (1-3). In P. aeruginosa, VIM-type enzymes are overall the most widespread and prevalent acquired MBLs (1, 4-7).Genes encoding VIM-type MBLs are usually carried on mobile gene cassettes associated with class 1 integron platforms (8), and integron-mediated cassette mobility has contributed to their dissemination, as indicated by the finding of bla VIM gene cassettes as part of different cassette arrays (9, 10). On the other hand, class 1 integron platforms are associated with functional or defective Tn402-like transposons, which preferentially target the res sites of plasmids and transposons of the Tn3 family (11-13), thus establishing genetic linkages that may further contribute to the mobility of the integron platforms (8).In P. aeruginosa VR-143/97, the bla VIM-1 index strain is...