Mechanisms responsible for imipenem resistance among Pseudomonas aeruginosa clinical isolates exposed to imipenem concentrations within the mutant selection window

Vassilara, Foula; Galani, Irene; Souli, Maria; Παπανικολάου, Κωνσταντίνος; Giamarellou, Helen; Παπαδοπουλοσ, Αντωνιοσ

doi:10.1016/j.diagmicrobio.2017.04.005

Cited by 12 publications

(9 citation statements)

References 40 publications

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“…(isolate 1442) and S278P (isolate 1631), the latter of which has been reported previously (31), were unique to these two imipenem/meropenem double -resistant isolates, although oprD frameshifts were also present in both cases ( Table 1). Two identical SNPs were observed in different isolates, one of which (Q402fs) surprisingly occurred independently in two isolates 1638 and 1664 belonging to separate phylogenetic lineages (ST379 and ST885, respectively, Table1 and Figure 1).…”

Section: Accepted Manuscriptsupporting

confidence: 62%

Phylogenetic analysis of resistance to ceftazidime/avibactam, ceftolozane/tazobactam and carbapenems in piperacillin/tazobactam-resistant Pseudomonas aeruginosa from cystic fibrosis patients

Zamudio

Hijazi

Joshi

et al. 2019

International Journal of Antimicrobial Agents

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Pseudomonas aeruginosa is one of the most important pathogens in cystic fibrosis. In this study we analysed the genetic basis and phylogenetic profile of resistance to ceftazidime/avibactam and ceftolozane/tazobactam as well as carbapenems in cystic fibrosis P. aeruginosa isolates. We conducted whole genome sequence analysis of a collection of isolates resistant to piperacillin/tazobactam from seven hospitals in Scotland since the introduction of these two cephalosporin/β-lactamase inhibitor combinations. Ceftazidime resistance was primarily related to AmpC induction, as tested by cloxacillin inhibition assays, while amino acid variations in AmpC were associated with high-level ceftazidime resistance not reversed by cloxacillin. Only isolates resistant to both ceftazidime/avibactam and ceftolozane/tazobactam carried AmpD mutations, likely resulting in ampC overexpression. All isolates resistant to ceftazidime/avibactam and/or ceftolozane/tazobactam were resistant to carbapenems and showed inactivating mutations in the chromosomal oprD gene. None of the isolates bore class A, B, D plasmid-encoded carbapenemases. Critically, we show that mutational resistance emerged in phylogenetically distant lineages suggesting that the mutations occur independently without conferring a selective advantage to any phylogenetic lineage. Our findings confirm the strong contribution of mutation-driven evolution to the population structure of P. aeruginosa. 1590 1664 88 5 256 256 12 8 A31V (n); V239 A(d); G242 R(d); G248 S(n) >3 2 2 Q402f s(d) A205 V(d), G300 A(n),

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Section: Accepted Manuscriptsupporting

confidence: 62%

Phylogenetic analysis of resistance to ceftazidime/avibactam, ceftolozane/tazobactam and carbapenems in piperacillin/tazobactam-resistant Pseudomonas aeruginosa from cystic fibrosis patients

Zamudio

Hijazi

Joshi

et al. 2019

International Journal of Antimicrobial Agents

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“…The oprD gene was found to be interrupted by the CLJ-ISL3 insertion (b), resulting in absence of the protein (Table S8). Loss-of-function mutations or deletions in oprD make the cell envelope impermeable to these antibiotics and have been repeatedly reported in isolates from patients undergoing treatment with imipenem or meropenem [52–55]. In addition, CLJ-ISL3 was detected in the 5′ portion of the ampD gene (), encoding the recycling amidase responsible for the production of muropeptide regulators of ampC expression [56, 57].…”

Section: Resultsmentioning

confidence: 99%

Insertion sequences drive the emergence of a highly adapted human pathogen

et al. 2020

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Pseudomonas aeruginosa is a highly adaptive opportunistic pathogen that can have serious health consequences in patients with lung disorders. Taxonomic outliers of P. aeruginosa of environmental origin have recently emerged as infectious for humans. Here, we present the first genome-wide analysis of an isolate that caused fatal haemorrhagic pneumonia. In two clones, CLJ1 and CLJ3, sequentially recovered from a patient with chronic pulmonary disease, insertion of a mobile genetic element into the P. aeruginosa chromosome affected major virulence-associated phenotypes and led to increased resistance to the antibiotics used to combat the infection. Comparative genome, proteome and transcriptome analyses revealed that this ISL3-family insertion sequence disrupted the genes for flagellar components, type IV pili, O-specific antigens, translesion polymerase and enzymes producing hydrogen cyanide. Seven-fold more insertions were detected in the later isolate, CLJ3, than in CLJ1, some of which modified strain susceptibility to antibiotics by disrupting the genes for the outer-membrane porin OprD and the regulator of β-lactamase expression AmpD. In the Galleria mellonella larvae model, the two strains displayed different levels of virulence, with CLJ1 being highly pathogenic. This study revealed insertion sequences to be major players in enhancing the pathogenic potential of a P. aeruginosa taxonomic outlier by modulating both its virulence and its resistance to antimicrobials, and explains how this bacterium adapts from the environment to a human host.

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“…Patagonin-CRISP was screened against various strains of microorganisms with liquid growth inhibition assay. The microbial strains chosen are drawn from snakes' oral cavities or are of medical and economic relevance (Hetru and Bulet, 1997;Vassilara et al, 2017;Yin et al, 2017;Ghosh et al, 2018;Yadav et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…The increased resistance of microorganisms to antimicrobial agents is a serious public health problem that has aroused the attention of the pharmaceutical industry and led it to search for new types of antibiotics. The failure of available antibiotics to contain certain pathogens indicates the need to develop more efficient and less toxic molecules from natural sources (Potron et al, 2015;Vassilara et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Patagonin-CRISP: Antimicrobial Activity and Source of Antimicrobial Molecules in Duvernoy’s Gland Secretion (Philodryas patagoniensis Snake)

et al. 2021

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Snake venom contains a variety of toxins with a range of biological activity, among these toxins cysteine-rich secreted proteins (CRISPs) can be found. The proteins of this family have masses of 20–30 kDa and display homologous amino acid sequences containing 16 cysteine residues, forming eight disulfide bonds. Some of these proteins have been explored, characterized, and described in terms of their activity; however, little is known about their range of activities. A search for new antimicrobial molecules is ongoing, as the number of microbial strains resistant to available antibiotics is increasing. We identified antimicrobial activity in the secretion of Duvernoy's gland of the rear-fanged Philodryas patagoniensis. Fractions of this venom were subjected to reverse-phase high performance liquid chromatography and analyzed to determine their antimicrobial activity with a liquid broth inhibition assay. One of the fractions presented activity against a Gram-negative bacterium and a filamentous fungus. This fraction was analyzed with LC-MS/MS, and a protein of 24,848.8 Da was identified. Database searches allowed us to identify it as a CRISP due to the presence of some unique fragments in the molecule. We called it patagonin-CRISP, as the same protein in the venom of P. patagoniensis had previously been characterized as having a different biological activity. Patagonin-CRISP presented activity at very low concentrations and showed no cytotoxic activity. This is the first time that antimicrobial activity has been identified for P. patagoniensis venom or for a CRISP family protein.

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Mechanisms responsible for imipenem resistance among Pseudomonas aeruginosa clinical isolates exposed to imipenem concentrations within the mutant selection window

Cited by 12 publications

References 40 publications

Phylogenetic analysis of resistance to ceftazidime/avibactam, ceftolozane/tazobactam and carbapenems in piperacillin/tazobactam-resistant Pseudomonas aeruginosa from cystic fibrosis patients

Phylogenetic analysis of resistance to ceftazidime/avibactam, ceftolozane/tazobactam and carbapenems in piperacillin/tazobactam-resistant Pseudomonas aeruginosa from cystic fibrosis patients

Insertion sequences drive the emergence of a highly adapted human pathogen

Patagonin-CRISP: Antimicrobial Activity and Source of Antimicrobial Molecules in Duvernoy’s Gland Secretion (Philodryas patagoniensis Snake)

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