Comprehensive genome data analysis establishes a triple whammy of carbapenemases, ICEs and multiple clinically-relevant bacteria

Abstract

28Carbapenemases inactivate most β-lactam antibiotics, including carbapenems and have 29 been frequently reported among Enterobacteriaceae, Acinetobacter spp. and 30 Pseudomonas spp. Traditionally, the horizontal gene transfer of carbapenemase-31 encoding genes (CEGs) has been linked to plasmids. However, given that integrative and 32 conjugative elements (ICEs) are possibly the most abundant conjugative elements 33 among prokaryotes, we conducted an in silico analysis to ascertain the likely role of ICEs 34 in the spread of CEGs among all bacterial genomes. We detected 7457 CEGs, of which 35 224 were located within putative ICEs among several clinically-relevant bacterial species 36 (including Klebsiella pneumoniae, Escherichia coli, Citrobacter freundii, Enterobacter 37 hormaechei and Pseudomonas aeruginosa). Most CEGs detected within ICEs belong to 38 the KPC, IMP and NDM families and different mechanisms were likely responsible for 39 acquisition of these genes. The majority of CEG-bearing ICEs belong to the MPFT, MPFF, 40 MPFG and MPFI classes and often encode additional adaptive traits such as resistance to 41 other antibiotics (e.g. aminoglycosides and fluoroquinolones), metal and biocide 42 tolerance and bacteriocin production. This study provides a snapshot of the different 43 CEGs associated with ICEs among all bacterial genomes and sheds light on the 44 underappreciated contribution of ICEs to the spread of carbapenem resistance globally.

Tn6603, a Carrier of Tn5053 Family Transposons, Occurs in the Chromosome and in a Genomic Island of Pseudomonas aeruginosa Clinical Strains

“…Moreover, pKLC102, PAGI-5, and PAGI-5v have conjugation-like functions, including a coupling protein (Orf34 of [ 6 ]) and relaxase (Orf2 of [ 6 ]), which are characteristic of the MPF G and MOB H -types, respectively. This integrase–MPF–relaxase combination has been described previously among ICEs [ 68 , 69 ]. Lastly, pilus proteins required for the conjugation mechanism of PAPI-1, and which are related to those of enterobacterial plasmid R64, have homologues in PAGI-5 (Orf80–Orf91 of [ 6 ]) and pKLC102 [ 70 ], as well as in PAGI-5v.…”

“…The latter feature suggests a capacity for lateral movement, and has been observed experimentally for several members of the pKLC102 family, which includes PAGI-5 [ 66 , 67 ]. Such movement is also supported on functional grounds, since these islands and PAGI-5v (e.g., in ST395, Figure 4 ) encode an integrase of the DNA_BRE_C-type (Orf1 of [ 6 ]) [ 68 ]. Moreover, pKLC102, PAGI-5, and PAGI-5v have conjugation-like functions, including a coupling protein (Orf34 of [ 6 ]) and relaxase (Orf2 of [ 6 ]), which are characteristic of the MPF G and MOB H -types, respectively.…”

Mobilome Analysis of Achromobacter spp. Isolates from Chronic and Occasional Lung Infection in Cystic Fibrosis Patients

“…MGEs have an important role in antimicrobial resistance and virulence [ 18 , 19 , 20 , 21 ] as well as in bacterial adaptation. Indeed, they encode genes related to these mechanisms and can enable their host to synthesize products that affect the fitness of co-infecting pathogens, like bacteriocins [ 22 , 23 ], or confer antibiotic resistance [ 24 ]. In particular, a strong link between ICEs and the dissemination of antibiotic resistance genes has been demonstrated [ 13 ].…”