Correlation between penicillin-binding protein 2 mutations and carbapenem resistance in Escherichia coli

Yamachika, Shinichiro; Sugihara, Chika; Kamai, Yasuki; Yamashita, Makoto

doi:10.1099/jmm.0.051631-0

Cited by 30 publications

(19 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gram-negative bacteria can express one or more resistance mechanisms, conferring resistance against antibiotics such as cephalosporins, aminoglycosides, quinolones and other classes of antimicrobials [52,53]. Bacterial infections caused by multidrug resistant pathogens have become more frequent, making the empiric therapeutic choice a true challenge [54].…”

Section: Discussionmentioning

confidence: 99%

Polydim-I antimicrobial activity against MDR bacteria and its model membrane interaction

et al. 2017

View full text Add to dashboard Cite

The rapid spread of multi-drug resistant pathogens represents a serious threat to public health, considering factors such as high mortality rates, treatment restrictions and high prevalence of multi-drug resistant bacteria in the hospital environment. Antimicrobial peptides (AMPs) may exhibit powerful antimicrobial activity against different and diverse microorganisms, also presenting the advantage of absence or low toxicity towards animal cells. In this study, the evaluation of the antimicrobial activity against multi-drug resistant bacteria of a recently described AMP from wasp, Polydim-I, was performed. Polydim-I presented activity against standard strains (non-carriers of multi-resistant genes) that are susceptible to commercial antimicrobials, and also against multi-drug resistant strains at concentrations bellow 1μg/ml (0.41 μM). This is a rather low concentration among those reported for AMPs. At this concentration we found out that Polydim-I inhibits almost 100% of the tested pathogens growth, while with the ATCC strains the minimum inhibitory concentration (MIC100) is 400 times higher. Also, in relation to in vitro activity of conventional drugs against multi-drug resistant bacteria strains, Polydim-I is almost 10 times more efficient and with broader spectrum. Cationic AMPs are known as multi-target compounds and specially for targeting the phospholipid matrix of bacterial membranes. Exploring the interactions of Polydim-I with lipid bilayers, we have confirmed that this interaction is involved in the mechanism of action. Circular dichroism experiments showed that Polydim-I undergoes a conformational transition from random coil to a mostly helical conformation in the presence of membrane mimetic environments. Zeta potential measurements confirmed the binding and partial charge neutralization of anionic asolectin vesicles, and also suggested a possible aggregation of peptide molecules. FTIR experiments confirmed that some peptide aggregation occurs, which is minimized in the presence of strongly anionic micelles of sodium dodecyl sulfate. Also, Polydim-I induced channel-like structures formation to asolectin lipid bilayers, as demonstrated in the electrophysiology experiments. We suggest that cationic Polydim-I targets the membrane lipids due to electrostatic attraction, partially accumulates, neutralizing the opposite charges and induces pore formation. Similar mechanism of action has already been suggested for other peptides from wasp venoms, especially mastoparans.

show abstract

Section: Discussionmentioning

confidence: 99%

Polydim-I antimicrobial activity against MDR bacteria and its model membrane interaction

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Therefore, we did not reassess the kinetics of PBP binding of carbapenems in this study. The rate of PBP‐carbapenem binding varies across bacterial species due to PBP differences and expression rates . As such, increased k on for porin entry is likely to promote enhanced target exposure and target association rates.…”

Section: Discussionmentioning

confidence: 99%

Structure-kinetic relationship of carbapenem antibacterials permeating throughE. coliOmpC porin

Tran¹,

Pearlstein²,

Williams³

et al. 2014

Proteins

View full text Add to dashboard Cite

The emergence of Gram-negative "superbugs" exhibiting resistance to known antibacterials poses a major public health concern. Low molecular weight Gram-negative antibacterials are believed to penetrate the outer bacterial membrane (OM) through porin channels. Therefore, intracellular exposure needed to drive antibacterial target occupancy should depend critically on the translocation rates through these proteins and avoidance of efflux pumps. We used electrophysiology to study the structure-translocation kinetics relationships of a set of carbapenem antibacterials through purified porin OmpC reconstituted in phospholipid bilayers. We also studied the relative susceptibility of OmpC+ and OmpC- E. coli to these compounds as an orthogonal test of translocation. Carbapenems exhibit good efficacy in OmpC-expressing E. coli cells compared with other known antibacterials. Ertapenem, which contains an additional acidic group compared to other analogs, exhibits the fastest entry into OmpC (k(on) ≈ 2 × 10(4) M(-1) s(-1)). Zwitterionic compounds with highly polar groups attached to the penem-2 ring, including panipenem, imipenem and doripenem exhibit faster k(on) (>10(4) M(-1) s(-1)), while meropenem and biapenem with fewer exposed polar groups exhibit slower k(on) (∼5 × 10(3) M(-1) s(-1)). Tebipenem pivoxil and razupenem exhibit ∼13-fold slower k(on) (∼1.5 × 10(3) M(-1) s(-1)) than ertapenem. Overall, our results suggest that (a) OmpC serves as an important route of entry of these antibacterials into E. coli cells; and (b) that the structure-kinetic relationships of carbapenem translocation are governed by H-bond acceptor/donor composition (in accordance with our previous findings that the enthalpic cost of transferring water from the constriction zone to bulk solvent increases in the presence of exposed nonpolar groups).

show abstract

“…[5,6] [7,8] A recent study indicates that mutations in a penicillin-binding protein may also play a role in carbapenem-resistance among E. coli. [9] The beta-lactam antibiotics include four main groups: penicillins, cephalosporins, monobactams and carbapenems.…”

Section: Beta-lactam Antibioticsmentioning

confidence: 99%

“…In paper II -V bacterial DNA preparation was amplified by amplification as described elsewhere followed by CTX-M gene specific PCR and subsequent amplicon sequencing. Obtained gene sequences were edited and compared with bla CTX-M DNA and bla CTX-Mlike DNA sequences using the bioinformatics freeware CLC in order to subgroup isolates into CTX-M groups 1,2,8,9 or 25. In paper II additional PCR amplification assays were carried out for detection of TEM-and SHV-genes.…”

Section: Detection Of Resistance Genesmentioning

confidence: 99%

“…Sixty-eight per cent of ESBL-producing E. coli was multi-resistant, and the most common multi-resistance pattern was the ESBL phenotype with decreased susceptibility to trimethoprim, trimethoprim-sulfamethoxazole, ciprofloxacin, gentamicin and tobramycin. Isolates belonging to CTX-M group 9 are generally more susceptible to antibiotics than the CTX-M group 1-producing E. coli.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae : Antibiotic consumption, Detection and Resistance Epidemiology

Balkhed¹

2014

View full text Add to dashboard Cite

Correlation between penicillin-binding protein 2 mutations and carbapenem resistance in Escherichia coli

Cited by 30 publications

References 29 publications

Polydim-I antimicrobial activity against MDR bacteria and its model membrane interaction

Polydim-I antimicrobial activity against MDR bacteria and its model membrane interaction

Structure-kinetic relationship of carbapenem antibacterials permeating throughE. coliOmpC porin

Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae : Antibiotic consumption, Detection and Resistance Epidemiology

Contact Info

Product

Resources

About