Upregulation of the clpB gene in response to heat shock and beta-lactam antibiotics in Acinetobacter baumannii

Lazaretti, Waleska Yana; Santos, Elaine Luzia dos; Silva, José Luis da Conceição; Kadowaki, Marina Kimiko; Gandra, Rinaldo Ferreira; Maller, Alexandre; Simão, Rita de Cássia Garcia

doi:10.1007/s11033-019-05209-4

Cited by 6 publications

(4 citation statements)

References 21 publications

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“…The extensive antibiotic resistance observed in A. baumannii is attributed to the presence and proliferation of multiple antibiotic-resistance genes. Numerous studies have documented the resistance of A. baumannii to most beta-lactam antibiotics (44,45) and quinolones (46,47), which is consistent with our findings. Additionally, there is a growing trend of resistance to aminoglycosides, as highlighted by Mortazavi et al (48).…”

Section: Discussionsupporting

confidence: 92%

Expression of Biofilm-Related Genes in Extensively Drug-Resistant Acinetobacter baumannii

Khosravy,

Hosseini,

Razavi

et al. 2023

Jundishapur J Microbiol

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Background: Acinetobacter baumannii is an important cause of nosocomial pneumonia in patients requiring long-term mechanical ventilation. Besides, extensively drug-resistant (XDR) strains cause infection in intensive care unit (ICU) patients. Chronic infections of A. baumannii and antimicrobial resistance are associated with biofilm formation. Several virulence genes, such as blaPER-1, pgaA, and bap, are involved in biofilm formation. Objectives: The current study examines the expression levels of biofilm formation-related genes in pneumonia patients. Methods: The sputum samples were collected from patients hospitalized in the ICU, and A. baumannii ATCC 19606, the reference strain, was isolated and cultured on blood agar, eosin methylene blue agar, and chocolate agar medium. The media were then incubated at 37°C for 18 - 24 hours. Next, Gram-Thirty XDR A. baumannii isolates were collected from the sputum samples of ICU patients at Besat Hospital in Tehran, Iran. Bacterial isolates were characterized for antibiotic resistance patterns and biofilm-forming ability. Subsequently, RNA was extracted from the biofilm-forming isolates. A real-time polymerase chain reaction (PCR) assay was performed to evaluate the expression levels of the blaPER-1, pgaA, and bap genes. Transcripts were normalized to 16S rRNA as an internal control, and gene expression fold changes were calculated. Statistical analysis was performed using an unpaired two-tailed t-test (P < 0.05) with SPSS (V. 16). Results: The disk diffusion susceptibility test revealed that all 30 (100%) isolates were resistant to piperacillin-tazobactam, cefepime, ceftriaxone, ceftazidime, gentamicin, imipenem, meropenem, levofloxacin, and ciprofloxacin. All 30 isolates from ICU-admitted patients (100%) were classified as XDR, and 27 (90%) isolates demonstrated the ability to form biofilms. The obtained results indicated a significant difference in gene expression levels. The fold change in expression for blaPER-1, bap, and pgaA was 7.473, 11.964, and 5.277, respectively. Conclusions: In our study, XDR A. baumannii primarily caused ventilator-associated pneumonia, and an observed increase in the expression of biofilm-related genes was noted in these strains. Healthcare centers should implement appropriate infection control programs to manage nosocomial infections, particularly in the ICU.

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Section: Discussionsupporting

confidence: 92%

Expression of Biofilm-Related Genes in Extensively Drug-Resistant Acinetobacter baumannii

Khosravy,

Hosseini,

Razavi

et al. 2023

Jundishapur J Microbiol

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“…faecalis following treatment with o -Phen, resulting in elongated or deformed, characterized by predominantly fusiform bacteria. Transcriptome sequencing results further validated this hypothesis, as key genes associated with bacterial decline, including degP (trypsin-like peptidase domain-containing protein), danK (encoding chromosomal DNA replication), and clpB (encoding protein refolding), were significantly downregulated. This disruption of bacterial homeostasis and cellular defense mechanisms led to the early onset of the decline phase .…”

Section: Discussionmentioning

confidence: 68%

Analyses of the Antibiofilm Activity of o-Phenanthroline Monohydrate against Enterococcus faecalis and Staphylococcus aureus and the Mechanisms Underlying These Effects

Wang,

Wu,

Wang

et al. 2024

ACS Infect. Dis.

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Enterococcus faecalis and Staphylococcus aureus exhibit robust biofilm formation capabilities, the formation of which is closely linked to pathogenicity and drug resistance, thereby resulting in host infection and treatment failure. o-Phenanthroline monohydrate (o-Phen) and its derivatives demonstrate a wide range of antibacterial and antifungal activities. In this study, we aimed to explore the antibiofilm activity of o-Phen to E. faecalis and S. aureus and provide insights into the molecular mechanisms for combating biofilm resistance. We demonstrated that o-Phen possesses significant antibacterial and antibiofilm properties against E. faecalis and S. aureus, inducing alterations in bacterial morphology, compromising cell membrane integrity, and exhibiting synergistic effects with β-lactam antibiotics at sub-MIC concentrations. The adhesion ability and automatic condensation capacity of, and synthesis of, extracellular polymers by E. faecalis cells were reduced by o-Phen, resulting in the inhibition of biofilm formation. Importantly, transcriptome analysis revealed 354 upregulated and 456 downregulated genes in o-Phen-treated E. faecalis. Differentially expressed genes were enriched in 11 metabolism-related pathways, including amino acid metabolism, pyrimidine metabolism, and glycolysis/gluconeogenesis. Moreover, the oppA, CeuA, and ZnuB genes involved in the ABC transport system, and the PBP1A penicillin-binding protein-coding genes sarA and mrcA were significantly downregulated. The multidrug efflux pump system and membrane permeability genes mdtG and hlyD, and bacterial adhesion-related genes, including adcA and fss2 were also downregulated, while mraZ and ASP23 were upregulated. Thus, o-Phen is anticipated to be an effective alternative drug for the treatment of E. faecalis and S. aureus biofilm-associated infections.

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“…It has previously been reported that protonophores, such as FCCP and DNP, can block translocation of periplasmic and membrane proteins in E. coli leading to aggregation and induced heat shock response with an increased level of the heat shock regulator protein sigma-32 (Jana et al 2009 ). The heat shock protease ClpP is implicated in this process (Jana et al 2009 ) and upregulation of the heat shock proteases has been linked to increased resistance to antimicrobial stress in Acinetobacter baumannii (Lazaretti et al 2020 )(Cardoso et al 2010 ) and E.coli (Yamaguchi et al 2003 )((Kohanski et al 2008 ). DNP has previously been shown to upregulate several heat shock responses in E. coli (Gage and Neidhardt 1993 ), so it is important to consider that DNP-induced stress response may contribute to the DNP-mediated increases in resistance to gentamicin observed herein (Figs.…”

Section: Discussionmentioning

confidence: 99%

Proton motive force underpins respiration-mediated potentiation of aminoglycoside lethality in pathogenic Escherichia coli

et al. 2022

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It is well known that loss of aerobic respiration in Gram-negative bacteria can diminish the efficacy of a variety of bactericidal antibiotics, which has lead to subsequent demonstrations that the formation of reactive oxygen species (ROS) and the proton motive force (PMF) can both play a role in antibiotic toxicity. The susceptibility of Gram-negative bacteria to aminoglycoside antibiotics, particularly gentamicin, has previously been linked to both the production of ROS and the rate of antibiotic uptake that is mediated by the PMF, although the relative contributions of ROS and PMF to aminoglycoside toxicity has remained poorly understood. Herein, gentamicin was shown to elicit a very modest increase in ROS levels in an aerobically grown Escherichia coli clinical isolate. The well-characterised uncoupler 2,4-dinitrophenol (DNP) was used to disrupt the PMF, which resulted in a significant decrease in gentamicin lethality towards E. coli. DNP did not significantly alter respiratory oxygen consumption, supporting the hypothesis that this uncoupler does not increase ROS production via elevated respiratory oxidase activity. These observations support the hypothesis that maintenance of PMF rather than induction of ROS production underpins the mechanism for how the respiratory chain potentiates the toxicity of aminoglycosides. This was further supported by the demonstration that the uncoupler DNP elicits a dramatic decrease in gentamicin lethality under anaerobic conditions. Together, these data strongly suggest that maintenance of the PMF is the dominant mechanism for the respiratory chain in potentiating the toxic effects of aminoglycosides.

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Upregulation of the clpB gene in response to heat shock and beta-lactam antibiotics in Acinetobacter baumannii

Cited by 6 publications

References 21 publications

Expression of Biofilm-Related Genes in Extensively Drug-Resistant Acinetobacter baumannii

Expression of Biofilm-Related Genes in Extensively Drug-Resistant Acinetobacter baumannii

Analyses of the Antibiofilm Activity of o-Phenanthroline Monohydrate against Enterococcus faecalis and Staphylococcus aureus and the Mechanisms Underlying These Effects

Proton motive force underpins respiration-mediated potentiation of aminoglycoside lethality in pathogenic Escherichia coli

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