Class C β-Lactamases: Molecular Characteristics

Philippon, A.; Arlet, Guillaume; Labia, Roger; Iorga, Bogdan I.

doi:10.1128/cmr.00150-21

Cited by 36 publications

(28 citation statements)

References 417 publications

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“…Those encoding the cephalosporinase AmpC (and all of their regulatory proteins AmpR, AmpD, AmpE, AmpG) were present in all the genomes; however, mutations in AmpC, AmpR, and AmpD were specific to the different subclades as observed for other species of Enterobacterales 13 ( Table S3 ). In addition to the highly conserved AmpC motifs (64SXSK, 150YXN, and 315KTG) and other conserved residues linked to the reference AmpC β-lactamase of Serratia SRT/SST, we observed amino acid variations at positions N86K and R91H in the “lineage Sn” linked to subclade 2B, apparently located in the middle of an alpha-helix (H) and a bend or turn 29,30 . A number of mutations (GC>AT) in the intergenic region between the ampC and ampR genes in these 2B isolates could have increased the number of stop codons affecting the half-life of AmpC and decreased the ability to degrade the antibiotic as suggested 31 .…”

Section: Resultsmentioning

confidence: 90%

Long-term dynamics of the “Serratia marcescenscomplex” in the hospital-built environment

Aracil-Gisbert,

Fernández-De-Bobadilla,

Guerra-Pinto

et al. 2023

Preprint

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Serratia marcescensis an opportunistic pathogen historically associated with abrupt, unpredictable, and severe outbreaks in hospital intensive care units (ICUs) and, more recently, with the spread of acquired genes encoding carbapenem resistance. However, the population biology and ecology ofS. marcescensin the hospital ecosystem is still poorly understood. Here, we combine epidemiological information of 1417Serratiaisolates collected from the sinks of a large ICU ward that underwent significant demographic and operational changes (2019-2020) and 99 non-redundant outbreak/non-outbreak isolates from the same hospital (2003-2019), with genomic data of 165 isolates. We first report hospital sinks as reservoirs of heterogeneous and coexistent populations of theS. marcescens complex(SMC). A novel SMC clade congruent with the recently describedSerratia neveispecies is predominant, exhibiting chromosomal AmpC β-lactamase with an unusual basal expression in contrast to one of the major features ofS. marcescens. PersistentSerratiasink strains are identical to those involved in clonal and polyclonal outbreaks of VIM-1 and OXA-48 producers since at least 2017. The 'source-sink' dynamics of SMC populations able to acquire the highly conserved plasmids such as IncL carryingblaVIM-1 orblaOXA-48 offer novel insights that might improve interventions to control outbreaks and treatSerratiainfections in high-risk hospital areas.

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Section: Resultsmentioning

confidence: 90%

Long-term dynamics of the “Serratia marcescenscomplex” in the hospital-built environment

Aracil-Gisbert,

Fernández-De-Bobadilla,

Guerra-Pinto

et al. 2023

Preprint

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“…Subsequently, energy minimization was performed using GROMOS96 implemented in Swiss PDB Viewer 4.1.0 [ 28 ]. Based on prior reports [ 29 , 30 , 31 , 32 ], three active sites of PDC were identified as follows: Ser62, Val63, Ser64, and Lys65 (here, motif 1), Tyr149, Ser150, and Asn151 (here, motif 2), Lys314, Thr315, and Gly316 (here, motif 3).…”

Section: Methodsmentioning

confidence: 99%

Molecular Evolutionary Analyses of the Pseudomonas-Derived Cephalosporinase Gene

et al. 2023

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Despite the increasing evidence of the clinical impact of Pseudomonas-derived cephalosporinase (PDC) sequence polymorphisms, the molecular evolution of its encoding gene, blaPDC, remains elusive. To elucidate this, we performed a comprehensive evolutionary analysis of blaPDC. A Bayesian Markov Chain Monte Carlo phylogenetic tree revealed that a common ancestor of blaPDC diverged approximately 4660 years ago, leading to the formation of eight clonal variants (clusters A–H). The phylogenetic distances within clusters A to G were short, whereas those within cluster H were relatively long. Two positive selection sites and many negative selection sites were estimated. Two PDC active sites overlapped with negative selection sites. In docking simulation models based on samples selected from clusters A and H, piperacillin was bound to the serine and the threonine residues of the PDC active sites, with the same binding mode for both models. These results suggest that, in P. aeruginosa, blaPDC is highly conserved, and PDC exhibits similar antibiotic resistance functionality regardless of its genotype.

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“…Furthermore, since A. baumannii has strong invasive virulence factors, such as outer membrane proteins, lipopolysaccharides and phospholipases, the treatment of A. baumannii infection has been regarded as a great threat to clinical practice [ 3 ]. Antibiotics such as carbapenems, β-lactam antibiotics and polymyxins, are commonly used clinically to treat A. baumannii infections [ 4 , 5 , 6 ]. However, the treatment of multi-drug resistant (MDR) A. baumannii is further aggravated by the abuse of antibiotics and the evolution of bacteria.…”

Section: Introductionmentioning

confidence: 99%

Acinetobacter Baumannii Phages: Past, Present and Future

et al. 2023

Viruses

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Acinetobacter baumannii (A. baumannii) is one of the most common clinical pathogens and a typical multi-drug resistant (MDR) bacterium. With the increase of drug-resistant A. baumannii infections, it is urgent to find some new treatment strategies, such as phage therapy. In this paper, we described the different drug resistances of A. baumannii and some basic properties of A. baumannii phages, analyzed the interaction between phages and their hosts, and focused on A. baumannii phage therapies. Finally, we discussed the chance and challenge of phage therapy. This paper aims to provide a more comprehensive understanding of A. baumannii phages and theoretical support for the clinical application of A. baumannii phages.

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Class C β-Lactamases: Molecular Characteristics

Cited by 36 publications

References 417 publications

Long-term dynamics of the “Serratia marcescenscomplex” in the hospital-built environment

Long-term dynamics of the “Serratia marcescenscomplex” in the hospital-built environment

Molecular Evolutionary Analyses of the Pseudomonas-Derived Cephalosporinase Gene

Acinetobacter Baumannii Phages: Past, Present and Future

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