Morphological changes induced by imipenem and meropenem at sub-inhibitory concentrations in Acinetobacter baumannii

Bernabéu-Wittel, Máximo; García-Curiel, A.; Pichardo, C.; Pachón-Ibáñez, María Eugenia; Me, Jiménez-Mejías; Pachón, Jerónimo

doi:10.1111/j.1469-0691.2004.00944.x

Cited by 10 publications

(10 citation statements)

References 17 publications

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“…Under increasing β-lactam concentrations, ovoid cells are typically observable until PBPs 1a and 1b [76,78,101] or PBPs 2 and 3 [85,110] become saturated, at which point the cells form spheroplasts and / or lyse depending on the PBPs affected and the osmolarity of the medium. The β-lactam induced formation of ovoid cells has been reported, not just in E. coli and P. aeruginosa, but in many species of Gram-negative bacteria including Acinetobacter baumanii [102], Klebsiella pneumoniae [54], Proteus mirabilis [54,111], and Serratia marcescens [54]. Again however, because PBP nomenclature is species-dependent [86], and because relatively few studies have determined the affinity of their test β-lactam(s) for the PBPs of their test organism(s), ovoid cell formation has not been attributed to inhibition of a specific PBP in these organisms.…”

Section: Ovoid Cellsmentioning

confidence: 99%

“…Nomenclature in the literature varies, some authors referring to them as'round forms' [76,100], 'round cells' [63, 101,102], 'spherical forms', 'spherical cells' [54,78,103], or 'coccoid forms' [104,105]. In a few papers, these descriptors are used interchangeably with the term 'spheroplast' [54,101,102] but this is incorrect. Unlike spheroplasts, ovoid cells are osmotically stable [63,75,76,100,106].…”

Section: Ovoid Cellsmentioning

confidence: 99%

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Morphological and ultrastructural changes in bacterial cells as an indicator of antibacterial mechanism of action

Cushnie

O’Driscoll

Lamb

2016

Cell. Mol. Life Sci.

149

124

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Section: Ovoid Cellsmentioning

confidence: 99%

Section: Ovoid Cellsmentioning

confidence: 99%

Morphological and ultrastructural changes in bacterial cells as an indicator of antibacterial mechanism of action

Cushnie

O’Driscoll

Lamb

2016

Cell. Mol. Life Sci.

149

124

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“…Exposure to meropenem (MEM) for two hours was shown to induce filamentation in both carbapenem-resistant P. aeruginosa mutants and their susceptible parents at this concentration [41]. At the IPM MIC, B. pseudomallei strains formed spheroplasts at an early growth phase, similar to A. baumannii [42]. These cells are morphologically typical of spheroplasts, with a near-perfect spherical shape and found as individuals rather than in cell arrangements like ovoid cells [43].…”

Section: Discussionmentioning

confidence: 99%

Optical microscopy reveals the dynamic nature of B. pseudomallei morphology during β-lactam antimicrobial susceptibility testing

McLaughlin

Bugrysheva

Sue

2020

Preprint

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BackgroundIn Gram-negative species, β-lactam antibiotics target penicillin binding proteins (PBPs) resulting in morphological alterations of bacterial cells. Observations of antibiotic-induced cell morphology changes can rapidly and accurately differentiate drug susceptible from resistant bacterial strains; however, resistant cells do not always remain unchanged. Burkholderia pseudomallei is a Gram-negative, biothreat pathogen and the causative agent of melioidosis, an often fatal infectious disease for humans.ResultsHere, we identified β-lactam targets in B. pseudomallei by in silico analysis. Ten genes encoding putative PBPs, including PBP-1, PBP-2, PBP-3 and PBP-6, were detected in the genomes of susceptible and resistant strains. Real-time, live-cell imaging of B. pseudomallei strains demonstrated dynamic morphological changes in broth containing clinically relevant β-lactam antibiotics. At sub-inhibitory concentrations of ceftazidime (CAZ), amoxicillin-clavulanic acid (AMC), and imipenem (IPM), filamentation, varying in length and proportion, was an initial response of the multidrug-resistant strain Bp1651 in exponential phase. However, a dominant morphotype reemerged during stationary phase that resembled cells unexposed to antibiotics. Similar morphology dynamics were observed for AMC-resistant strains, MSHR1655 and 724644, when exposed to sub-inhibitory concentrations of AMC. For all B. pseudomallei strains evaluated, increased exposure time and exposure to increased concentrations of AMC at and above minimal inhibitory concentrations (MICs) in broth resulted in cell morphology shifts from filaments to spheroplasts and/or cell lysis. B. pseudomallei morphology changes were more consistent in IPM. Spheroplast formation followed by cell lysis was observed for all strains in broth containing IPM at concentrations greater than or equal to MICs, however, the time to cell lysis was variable. Length of B. pseudomallei cells was strain-, drug- and drug concentration-dependent.ConclusionsBoth resistant and susceptible B. pseudomallei strains exhibited filamentation during early exposure to AMC and CAZ at concentrations used to interpret susceptibility (based on CLSI guidelines). While developing a rapid β-lactam antimicrobial susceptibility test based on cell-shape alone requires more extensive analyses, optical microscopy detected B. pseudomallei growth attributes that lend insight into antibiotic response and antibacterial mechanisms of action.

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“…When it comes to combination with other antibiotics, colistin is known to induce damage to the cell-wall structures of Gram-negative bacteria, thereby allowing the accelerated penetration of rifampicin (Song et al, 2008;Aoki et al, 2009). Moreover, Bernabeu-Wittel et al (2004) reported that meropenem at sub-MIC levels induced spheroplastic changes (.3 mm in size) of A. baumannii isolates, which might also increase the intracellular penetration of rifampicin. …”

Section: Discussionmentioning

confidence: 99%

Clinical and microbiological characterization of carbapenem-resistant Acinetobacter baumannii bloodstream infections

Song

Cheong

Choi

et al. 2011

Journal of Medical Microbiology

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The incidence of carbapenem-resistant Acinetobacter baumannii infection is increasing, which might be associated with high morbidity and mortality among critically ill patients with limited therapeutic options. This study was conducted to evaluate the clinical and microbiological features of carbapenem-resistant A. baumannii bacteraemia. The medical records of 28 adult patients with this bacteraemia admitted to Korea University Guro Hospital, from January 2005 through December 2010, were reviewed. Using the 28 bloodstream isolates, we intended to detect genes encoding carbapenemases, and investigate the inoculum effect on each of the antimicrobial agents rifampicin, imipenem, colistin and tigecycline. With one blood isolate from a patient with pneumonia, rifampicin-inducible resistance was examined using the experimental mouse pneumonia model. Out of 28 carbapenem-resistant A. baumannii bloodstream infections (BIs), the most common primary focus was the central venous catheter (35.7 %) and then the lung (32.1 %). The 30 day overall mortality was 53.6 %; in most cases (80 %) the patients died within 10 days after the onset of the bacteraemia. By univariate analysis, inappropriate antimicrobial therapy (73.3 vs 30.8 %, P50.02), mechanical ventilation (53.3 vs 15.4 %, P50.04) and a high Pitt bacteraemia score (4.9±1.9 vs 2.2±1.2, P,0.01) were statistically significant risk factors for mortality, while only a high Pitt bacteraemia score (odds ratio 2.6; 95 % confidence interval 1.1-6.5) was independently associated with 30 day mortality by multivariate analysis. All 28 isolates had the bla OXA-51 -like gene with upstream ISAbaI, 2 of which additionally had the bla OXA-58 -like gene and the bla OXA-23 -like gene. Inoculum effect and rifampicin inducible resistance were not detected. Considering the rapid progression to death in carbapenemresistant A. baumannii BIs, early empirical antibiotic therapy would be warranted based on the local microbiological data in each hospital.

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Morphological changes induced by imipenem and meropenem at sub-inhibitory concentrations in Acinetobacter baumannii

Cited by 10 publications

References 17 publications

Morphological and ultrastructural changes in bacterial cells as an indicator of antibacterial mechanism of action

Morphological and ultrastructural changes in bacterial cells as an indicator of antibacterial mechanism of action

Optical microscopy reveals the dynamic nature of B. pseudomallei morphology during β-lactam antimicrobial susceptibility testing

Clinical and microbiological characterization of carbapenem-resistant Acinetobacter baumannii bloodstream infections

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