Tigecycline Resistance-Associated Mutations in the MepA Efflux Pump in Staphylococcus aureus

Huang, Hui-qin; Wan, Peng; Luo, Xinyue; Lu, Yixing; Li, Xiaoshen; Xiong, Wenguang; Zeng, Zhenling

doi:10.1128/spectrum.00634-23

Cited by 6 publications

(2 citation statements)

References 36 publications

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“…A single B/GBS Int 9.2 prophage was found to carry a gene encoding a multidrug and toxic compound extrusion (MATE)-like protein, similar to MepA from Staphylococcus aureus [41]. It has been reported that expression of MATE proteins in bacteria confers resistance to toxic dyes and multiple antibiotics [42,43].…”

Section: Discussionmentioning

confidence: 99%

Revisiting typing systems for group BStreptococcus(GBS) prophages: an application in prophage detection and classification in GBS isolates from Argentina

Kovacec,

Di Gregorio,

Pajón

et al. 2024

Preprint

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Group B Streptococcus (GBS) causes severe infections in neonates and adults with comorbidities. Prophages have been reported to contribute to GBS evolution and pathogenicity. However, no studies are available to date on the presence and diversity of prophages in GBS isolates from humans in South America. This study provides insights into the prophage content of 365 GBS isolates collected from clinical samples in the context of an Argentinean multicentric study. Using whole genome sequence data, we implemented two previously proposed methods for prophage typing: a PCR approach (carried out in silico) coupled with a blastx-based method to classify prophages based on their prophage group and integrase type, respectively. We manually searched the genomes and identified 325 prophages. However, only 80% of prophages could be accurately categorised with the previous approaches. Integration of phylogenetic analysis, prophage group and integrase type allowed for all to be classified into 19 prophage types, which correlated with GBS clonal complex grouping. The revised prophage typing approach was additionally improved by using a blastn search after enriching the database with 10 new genes for prophage group classification combined with the existing integrase typing method. This modified and integrated typing system was applied to the analysis of 615 GBS genomes (365 GBS from Argentina and 250 from public databases), which revealed 29 prophage types, including 2 novel integrase subtypes. Their characterization and comparative analysis revealed major differences in the lysogeny and replication modules. Genes related to bacterial fitness, virulence or adaptation to stressful environments were detected in all prophage types. Considering prophage prevalence, distribution and their association with bacterial virulence, it is important to study their role in GBS epidemiology. In this context, we propose the use of an improved and integrated prophage typing system suitable for rapid phage detection and classification with little computational processing.

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Section: Discussionmentioning

confidence: 99%

Revisiting typing systems for group BStreptococcus(GBS) prophages: an application in prophage detection and classification in GBS isolates from Argentina

Kovacec,

Di Gregorio,

Pajón

et al. 2024

Preprint

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“…This study's results confirm a similar synergistic effect in the Gram-positive bacterium S. aureus. The S. aureus ATCC 33593 contains four genes (mepA, norA, norB, and sdrM) encoding antibiotic efflux pumps; MepA is known to efflux aminoglycosides and fluoroquinolone antibiotics [3,43]. Tobramycin is an aminoglycoside, and it has been suggested that tobramycin is effluxed by MepA.…”

Section: Corydalis Tuber Extract and Berberine Are Efflux Pump Inhibi...mentioning

confidence: 99%

Enhanced Efficacy of Ciprofloxacin and Tobramycin against Staphylococcus aureus When Combined with Corydalis Tuber and Berberine through Efflux Pump Inhibition

Seo,

Kim,

Kim

2024

Antibiotics

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One way that bacteria develop antibiotic resistance is by reducing intracellular antibiotic concentrations through efflux pumps. Therefore, enhancing the efficacy of antibiotics using efflux pump inhibitors provides a way to overcome this type of resistance. Notably, an increasing number of pathogenic Staphylococcus aureus strains have efflux pump genes. In this study, the extract from Corydalis ternata Nakai tuber (Corydalis Tuber) at 512 mg/L was demonstrated to have an antibiotic synergistic effect with ciprofloxacin at 2 mg/L and tobramycin at 1024 mg/L against methicillin-resistant S. aureus (MRSA). Berberine, an isoquinoline alkaloid identified in Corydalis Tuber, was identified as contributing to this effect. Ethidium bromide efflux pump activity assays showed that Corydalis Tuber extract and berberine inhibited efflux, suggesting that they are efflux pump inhibitors. Molecular docking simulations suggested that berberine binds to S. aureus efflux pump proteins MepA, NorA, NorB, and SdrM. Additionally, berberine and Corydalis Tuber extract inhibit biofilm formation, which can confer antibiotic resistance. This study’s findings suggest that Corydalis Tuber, a traditional herbal medicine, and berberine, a medicinal supplement, act as S. aureus efflux pump inhibitors, synergistically increasing the efficacy of ciprofloxacin and tobramycin and showing promise as a treatment for antibiotic-resistant S. aureus infections, including MRSA.

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Antimicrobial activity of eravacycline and other comparative agents on aerobic and anaerobic bacterial pathogens in Taiwan: A clinical microbiological study

Tsai,

Chen,

Chang

et al. 2024

Journal of Global Antimicrobial Resistance

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Tigecycline Resistance-Associated Mutations in the MepA Efflux Pump in Staphylococcus aureus

Abstract: Previous analysis has shown that overexpression of MepA is an exact mechanism involved in tigecycline resistance apart from the rpsJ mutation and is usually dependent on the mutant mepR . However, no research has evaluated the effects of diverse mutations discovered in TRSA in MepA.

Cited by 6 publications

References 36 publications

Revisiting typing systems for group BStreptococcus(GBS) prophages: an application in prophage detection and classification in GBS isolates from Argentina

Revisiting typing systems for group BStreptococcus(GBS) prophages: an application in prophage detection and classification in GBS isolates from Argentina

Enhanced Efficacy of Ciprofloxacin and Tobramycin against Staphylococcus aureus When Combined with Corydalis Tuber and Berberine through Efflux Pump Inhibition

Antimicrobial activity of eravacycline and other comparative agents on aerobic and anaerobic bacterial pathogens in Taiwan: A clinical microbiological study

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