Concentration-dependency of β-lactam-induced filament formation in Gram-negative bacteria

Abstract

Ceftazidime and cefotaxime are beta-lactam antibiotics with dose-related affinities for penicillin-binding protein (PBP)-3 and PBP-1. At low concentrations, these antibiotics inhibit PBP-3, leading to filament formation. Filaments are long strands of non-dividing bacteria that contain enhanced quantities of endotoxin molecules. Higher concentrations of ceftazidime or cefotaxime cause inhibition of PBP-1, resulting in rapid bacterial lysis, which is associated with low endotoxin release. In the present study, 37 isolates of Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa and Acinetobacter spp. were studied over a 4-h incubation period in the presence of eight concentrations of ceftazidime or cefotaxime. As resistance of Gram-negative bacteria is an emerging problem in clinical practice, 14 isolates of E. coli and Klebsiella pneumoniae that produced extended-spectrum beta-lactamases (ESBLs) were also investigated. Morphological changes after exposure to the beta-lactam antibiotics revealed recognisable patterns in various bacterial families, genera and isolates. In general, all isolates of Enterobacteriaceae produced filaments within a relatively small concentration range, with similar patterns for E. coli and K. pneumoniae. Pseudomonas and Acinetobacter spp. produced filaments in the presence of clinically-relevant concentrations of both antibiotics as high as 50 mg/L. In all genera, filament-producing capacity was clearly related to the MIC. Ceftazidime induced filament production in more isolates and over wider concentration ranges than did cefotaxime. Interestingly, ESBL-producing isolates were not protected against filament induction. The induction of filament production may lead to additional risks during empirical treatment of severe infections.

Molecular Mechanisms of Sulbactam Antibacterial Activity and Resistance Determinants in Acinetobacter baumannii

“…2B) formed "spaghetti-like" filaments, quite similar to the well-established phenotype observed upon treatment with ceftazidime and aztreonam ( Fig. 2C and D) (41) and consistent with their similar mechanisms of PBP inhibition. In contrast, treatment of A. baumannii with 0.5ϫ MIC of meropenem resulted in spheroplasts that were larger and more rounded (Fig.…”

Effects of Mushroom and Chicory Extracts on the Physiology and Shape of Prevotella intermedia, a Periodontopathogenic Bacterium

“…Thus, a mode of action comparable with that of antibiotics may be supposed for these natural extracts. This statement is further supported by the observation that sub-MICs display morphogenetic effects such as those induced by the MIC and higher doses, as previously demonstrated for both β -lactams and quinolones [16, 18]. Thus, this preliminary report indicates that a specific mode of action exists and the identification of specific target(s) is needed.…”

Effects of mushroom and chicory extracts on the shape, physiology and proteome of the cariogenic bacterium Streptococcus mutans

“…mutans cells are indeed similar to those observed in streptococcal thermo-sensitive division mutants when incubated at non-permissive temperature or exposed to both sub- and inhibitory doses of β-lactam antibiotics [26]. These considerations as a whole lend further support to the hypothesis that the mode of action is comparable to that of antimicrobial families such as quinolones and β-lactams, thus, an antibiotic-like mode of action is suggested for these compounds [25,27,28]. …”