Identifying the effect of vancomycin on health care–associated methicillin-resistant <i>Staphylococcus aureus</i> strains using bacteriological and physiological media

Rajput, Abhishek; Poudel, Saugat; Tsunemoto, Hannah; Meehan, Michael J.; Szubin, Richard; Olson, Connor A.; Seif, Yara; Lamsa, Anne; Dillon, Nicholas; Vrbanac, Alison; Sugie, Joseph; Dahesh, Samira; Monk, Jonathan M.; Dorrestein, Pieter C.; Knight, Rob; Pogliano, Joe; Nizet, Victor; Feist, Adam M.; Palsson, Bernhard Ø.

doi:10.1093/gigascience/giaa156

Cited by 8 publications

(5 citation statements)

References 30 publications

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“…The iModulon SoxR, for example, contains the genes mexGHI and ompD ( Figure 3c ) and has upregulated activity during treatment with beta-lactam antibiotics in R10LB and downregulated activity in CAMHB ( Figure 3a ), which correlates with the observed differences in MIC. The difference in the MIC value of antibiotics in both media types were also found in our previous studies on Staphylococcus aureus 33–35 . Similarly, there was increased activity of the iModulon CzcR, involved in divalent cation homeostasis 36 , in R10LB compared to CAMHB ( Figure 3a ).…”

Section: Resultssupporting

confidence: 84%

Advanced transcriptomic analysis reveals the role of efflux pumps and media composition in antibiotic responses ofPseudomonas aeruginosa

Rajput

Tsunemoto

Sastry

et al. 2022

Preprint

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Pseudomonas aeruginosa is an opportunistic pathogen and major cause of hospital acquired infections. The pathogenicity and virulence of P. aeruginosa is largely determined by its transcriptional regulatory network (TRN). We used 411 transcription profiles of P. aeruginosa from diverse growth conditions to construct a quantitative TRN by identifying independently modulated sets of genes (called iModulons) and their condition-specific activity levels. The current study focused on the use of iModulons to analyze pathogenicity and antibiotic resistance of P. aeruginosa. Our analysis revealed: 1) 116 iModulons, 81 of which show strong association with known regulators; 2) novel roles of two-component systems in regulating antibiotics efflux pumps; 3) substrate-efflux pump associations; 4) differential iModulon activity in response to beta-lactam antibiotics in bacteriological and physiological media; 5) differential activation of ‘Cell Division’ iModulon resulting from exposure to different beta-lactam antibiotics; and 6) a role of the PprB iModulon in the stress-induced transition from planktonic to biofilm lifestyle. In light of these results, the construction of an iModulon-based TRN provides a transcriptional regulatory basis for key aspects of P. aeruginosa infection, such as antibiotic stress responses and biofilm formation. Taken together, our results offer a novel mechanistic understanding of P. aeruginosa pathogenicity.SignificanceLarge data sets and machine learning are impacting a growing number of areas of research in the life sciences. Once the compendia of bacterial transcriptomes reached a critical size, we could use source signal extraction algorithms to find lists of co-regulated genes (called iModulons) associated with a transcription factor (TF) to them. The gene composition of iModulons and their condition-dependent activity levels constitute a quantitative description of the composition of bacterial transcriptomes. This study shows how this approach can be used to reveal the responses of P. aeruginosa to antibiotics and thus yield a deep regulatory understanding of pathogenicity properties. This study motivates the execution of similar studies for the other ESKAPEEs to yield a broad understanding of the role of TRNs in antibiotic responses to these urgent threat bacterial pathogens.

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Section: Resultssupporting

confidence: 84%

Advanced transcriptomic analysis reveals the role of efflux pumps and media composition in antibiotic responses ofPseudomonas aeruginosa

Rajput

Tsunemoto

Sastry

et al. 2022

Preprint

Self Cite

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“…The iModulon SoxR, for example, contains the genes mexGHI and omp D (Figure 3C ) and has upregulated activity during treatment with beta-lactam antibiotics in R10LB and downregulated activity in CAMHB (Figure 3A ), which correlates with the observed differences in MIC. The difference in the MIC value of antibiotics in both media types were also found in our previous studies on Staphylococcus aureus ( 57–59 ). Similarly, there was increased activity of the iModulon CzcR/Fur, involved in divalent cation homeostasis ( 60 ), in R10LB compared to CAMHB (Figure 3A ).…”

Section: Resultssupporting

confidence: 84%

Advanced transcriptomic analysis reveals the role of efflux pumps and media composition in antibiotic responses ofPseudomonas aeruginosa

Rajput

Tsunemoto

Sastry

et al. 2022

Nucleic Acids Research

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Pseudomonas aeruginosa is an opportunistic pathogen and major cause of hospital-acquired infections. The virulence of P. aeruginosa is largely determined by its transcriptional regulatory network (TRN). We used 411 transcription profiles of P. aeruginosa from diverse growth conditions to construct a quantitative TRN by identifying independently modulated sets of genes (called iModulons) and their condition-specific activity levels. The current study focused on the use of iModulons to analyze the biofilm production and antibiotic resistance of P. aeruginosa. Our analysis revealed: (i) 116 iModulons, 81 of which show strong association with known regulators; (ii) novel roles of regulators in modulating antibiotics efflux pumps; (iii) substrate-efflux pump associations; (iv) differential iModulon activity in response to beta-lactam antibiotics in bacteriological and physiological media; (v) differential activation of ‘Cell Division’ iModulon resulting from exposure to different beta-lactam antibiotics and (vi) a role of the PprB iModulon in the stress-induced transition from planktonic to biofilm lifestyle. In light of these results, the construction of an iModulon-based TRN provides a transcriptional regulatory basis for key aspects of P. aeruginosa infection, such as antibiotic stress responses and biofilm formation. Taken together, our results offer a novel mechanistic understanding of P. aeruginosa virulence.

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“…S. aureus is a common cause of community and hospital-acquired infection ( 58 , 59 ). The WHO has regarded it as one of the primary clinical concerns, due to the global recognition of MRSA as a public health issue and the antibiotic resistance pattern of MRSA ( 60 ).…”

Section: Discussionmentioning

confidence: 99%

Current molecular approach for diagnosis of MRSA: a meta-narrative review

Sim

Lee

Abushelaibi

et al. 2022

dti

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Introduction: Detection and diagnosis of MRSA are important in ensuring a correct and effective treatment, further reducing its spread. There are a wide range of molecular approaches for the diagnosis of AMR in MRSA, including PCR, MLST and SCCmec. This review aims to study and appraise current molecular diagnostic methods used for the detection of MRSA. Method: This narrative review was performed by searching the PubMed using the following search terms: (molecular diagnosis) AND (antimicrobial resistance) NOT (review [publication type)) NOT (systematic review [publication type)) NOT (meta-analysis[publication type)) AND (methicillin-resistant staphylococcus aureus). Studies using molecular diagnostic techniques for the detection of MRSA were included, while non-English language, duplicates, and non-article studies were excluded. After reviewing the libraries and a further manual search, 20 studies were included in this paper. RAMESES publication standard for narrative reviews was used for this synthesis. Results: Of the 20 studies included, 11 studies employed PCR for diagnosing MRSA , 2 studies on DNA Microarray, Xpert MRSA/SA BC assay (n=1), MALDI-TOF (n=2), MLST (n=5) and SCCMec typing (n=1). Discussion: Different diagnostic methods used for the diagnosis of MRSA have been studied in this review. Each diagnostic technique have its benefits and drawbacks, however, this study concludes that PCR has been extensively used due to its increased sensitivity and cost-effectiveness.

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Identifying the effect of vancomycin on health care–associated methicillin-resistant Staphylococcus aureus strains using bacteriological and physiological media

Cited by 8 publications

References 30 publications

Advanced transcriptomic analysis reveals the role of efflux pumps and media composition in antibiotic responses ofPseudomonas aeruginosa

Advanced transcriptomic analysis reveals the role of efflux pumps and media composition in antibiotic responses ofPseudomonas aeruginosa

Advanced transcriptomic analysis reveals the role of efflux pumps and media composition in antibiotic responses ofPseudomonas aeruginosa

Current molecular approach for diagnosis of MRSA: a meta-narrative review

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