Proteomic Analyses of Acinetobacter baumannii Clinical Isolates to Identify Drug Resistant Mechanism

Wang, Ping; Li, Ren-Qing; Wang, Lei; Yang, Wentao; Zhou, Qinghua; Xiao, Di

doi:10.3389/fcimb.2021.625430

Cited by 15 publications

(13 citation statements)

References 113 publications

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“…Therefore, many recent studies report the proteomic pro les or proteomes of drug-resistant clinical isolates as well as bacteria with drug resistance which was induced in the laboratory. [13][14][15][16][17] Typically, the whole proteome is measured and to show differential expression of numerous proteins in various drug-resistant bacteria, including those related to metabolism, reactive oxygen species management, drug targets, DNA/RNA modi cation, etc. In the case of the proteomes of antibiotic-resistant Ab strains, researchers observed that β-lactamase expression was generally upregulated.…”

Section: Introductionmentioning

confidence: 99%

A novel strategy to characterize the pattern of β-lactam antibiotic-induced drug resistance in Acinetobacter baumannii

Hillyer

Benin

Sun

et al. 2023

Preprint

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Carbapenem-resistant Acinetobacter baumannii (CRAb) is an urgent public health threat, according to the CDC. This pathogen has few treatment options and causes severe nosocomial infections with > 50% fatality rate. Although previous studies have examined the proteome of CRAb, there have been no focused analyses of dynamic changes to β-lactamase expression that may occur due to drug exposure. Here, we present our initial proteomic study of variation in β-lactamase expression that occurs in CRAb with different β-lactam antibiotics. Briefly, drug resistance to Ab (ATCC 19606) was induced by the administration of various classes of β-lactam antibiotics, and the cell-free supernatant was isolated, concentrated, separated by SDS-PAGE, digested with trypsin, and identified by label-free LC-MS-based quantitative proteomics. Peptides were identified and evaluated using a 1789 sequence database of Ab β-lactamases from UniProt. Importantly, we observed that different antibiotics, even those of the same class (e.g. penicillin and amoxicillin), induce non-equivalent responses comprising various Class C and D serine-β-lactamases, resulting in unique resistomes. These results open the door to a new approach of analyzing and studying the problem of multi-drug resistance in bacteria that rely strongly on β-lactamase expression.

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Section: Introductionmentioning

confidence: 99%

A novel strategy to characterize the pattern of β-lactam antibiotic-induced drug resistance in Acinetobacter baumannii

Hillyer

Benin

Sun

et al. 2023

Preprint

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“…Examples of these are found in class A and D serine β-lactamases and class B metallo-β-lactamases, with the class D OXA-type serine β-lactamase being regularly detected in CRAb 17 – 19 . Previous studies have also reported that a variety of such OXA-type β-lactamases can be found in CRAb 19 ; however, there has been limited work done on attempting to selectively characterize the entire set of β-lactamases in a single strain and compare these with resistant mutants 20 – 23 .…”

Section: Introductionmentioning

confidence: 99%

A novel strategy to characterize the pattern of β-lactam antibiotic-induced drug resistance in Acinetobacter baumannii

Hillyer

Benin

Sun

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Carbapenem-resistant Acinetobacter baumannii (CRAb) is an urgent public health threat, according to the CDC. This pathogen has few treatment options and causes severe nosocomial infections with > 50% fatality rate. Although previous studies have examined the proteome of CRAb, there have been no focused analyses of dynamic changes to β-lactamase expression that may occur due to drug exposure. Here, we present our initial proteomic study of variation in β-lactamase expression that occurs in CRAb with different β-lactam antibiotics. Briefly, drug resistance to Ab (ATCC 19606) was induced by the administration of various classes of β-lactam antibiotics, and the cell-free supernatant was isolated, concentrated, separated by SDS-PAGE, digested with trypsin, and identified by label-free LC–MS-based quantitative proteomics. Thirteen proteins were identified and evaluated using a 1789 sequence database of Ab β-lactamases from UniProt, the majority of which were Class C β-lactamases (≥ 80%). Importantly, different antibiotics, even those of the same class (e.g. penicillin and amoxicillin), induced non-equivalent responses comprising various isoforms of Class C and D serine-β-lactamases, resulting in unique resistomes. These results open the door to a new approach of analyzing and studying the problem of multi-drug resistance in bacteria that rely strongly on β-lactamase expression.

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“…The Gram-negative aerobic, non-motile, pleomorphic bacillus Acinetobacter baumannii [ 1 ] is a multidrug-resistant opportunistic pathogen, currently identified as one of the major causes of nosocomial infections in the healthcare system worldwide [ 2 ]. Moubareck et al defined A. baumannii as the main causative agent of pneumonia, sepsis, meningitis and urinary tract and wound infections [ 3 ], with it being correlated to a nosocomial mortality rate of up to 35% [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Recent Progress in Phage Therapy to Modulate Multidrug-Resistant Acinetobacter baumannii, including in Human and Poultry

et al. 2022

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Acinetobacter baumannii is a multidrug-resistant and invasive pathogen associated with the etiopathology of both an increasing number of nosocomial infections and is of relevance to poultry production systems. Multidrug-resistant Acinetobacter baumannii has been reported in connection to severe challenges to clinical treatment, mostly due to an increased rate of resistance to carbapenems. Amid the possible strategies aiming to reduce the insurgence of antimicrobial resistance, phage therapy has gained particular importance for the treatment of bacterial infections. This review summarizes the different phage-therapy approaches currently in use for multiple-drug resistant Acinetobacter baumannii, including single phage therapy, phage cocktails, phage–antibiotic combination therapy, phage-derived enzymes active on Acinetobacter baumannii and some novel technologies based on phage interventions. Although phage therapy represents a potential treatment solution for multidrug-resistant Acinetobacter baumannii, further research is needed to unravel some unanswered questions, especially in regard to its in vivo applications, before possible routine clinical use.

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Proteomic Analyses of Acinetobacter baumannii Clinical Isolates to Identify Drug Resistant Mechanism

Cited by 15 publications

References 113 publications

A novel strategy to characterize the pattern of β-lactam antibiotic-induced drug resistance in Acinetobacter baumannii

A novel strategy to characterize the pattern of β-lactam antibiotic-induced drug resistance in Acinetobacter baumannii

A novel strategy to characterize the pattern of β-lactam antibiotic-induced drug resistance in Acinetobacter baumannii

Recent Progress in Phage Therapy to Modulate Multidrug-Resistant Acinetobacter baumannii, including in Human and Poultry

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