SarA plays a predominant role in controlling the production of extracellular proteases in the diverse clinical isolates of<i>Staphylococcus aureus</i>LAC and UAMS-1

Ramirez, Aura M; Beenken, Karen E.; Byrum, Stephanie D.; Tackett, Alan J.; Shaw, Lindsey N.; Gimza, Brittney D.; Smeltzer, Mark S.

doi:10.1080/21505594.2020.1855923

Cited by 17 publications

(47 citation statements)

References 89 publications

(206 reference statements)

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“…These data demonstrate that the method is suited to effectively assess positive and negative regulatory connections. In agreement with the known role of SarA as a repressor of aureolysin transcription [28, 33, 34], we observed a large increase in bioluminescence in the sarA ::Tn strain (, well D5), thereby validating our method. For a mutant of the redox-sensing transcriptional repressor, rex , a decrease in bioluminescence was observed (, well A6).…”

Section: Methodology and Discussionsupporting

confidence: 88%

Screening transcriptional connections in Staphylococcus aureus using high-throughput transduction of bioluminescent reporter plasmids

et al. 2022

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Characterization of transcriptional networks is one of the main strategies used to understand how bacteria interact with their environment. To reveal novel regulatory elements in the human pathogen Staphylococcus aureus , we adapted a traditional transduction protocol to be used in a high-throughput format in combination with the publicly available S. aureus Nebraska Transposon Mutant Library. Specifically, plasmid transductions are performed in 96-well format, so that a single plasmid can be simultaneously transferred into numerous recipient strains. When used in conjunction with bioluminescent reporter constructs, this strategy enables parallel and continuous monitoring of downstream transcriptional effects of hundreds of defined mutations. Here, we use this workflow in a proof-of-concept study to identify novel regulators of the staphylococcal metalloprotease aureolysin. Importantly, this strategy can be utilized with any other bacterium where plasmid transduction is possible, making it a versatile and efficient tool to probe transcriptional regulatory connections.

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Section: Methodology and Discussionsupporting

confidence: 88%

Screening transcriptional connections in Staphylococcus aureus using high-throughput transduction of bioluminescent reporter plasmids

et al. 2022

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“…Lincomycin was also included in Ery agar at 25 μg/ml. Mutants deficient in either sspA (encoding V8 protease) or all ten secreted proteases (Δ sspA and Δprotease, respectively) have been previously described ( Kolar et al, 2013 ; Ramirez et al, 2020 ). Strains deficient in the spa gene were produced as part of this study, using the Nebraska Transposon Mutant Library (NTML) and the NTML standard protocol to switch the erythromycin (ery) resistance cassette to tetracycline (tet) resistance ( Fey et al, 2013 ).…”

Section: Methodsmentioning

confidence: 99%

Insight into the human pathodegradome of the V8 protease from Staphylococcus aureus

2021

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SUMMARY Staphylococcus aureus possesses ten extracellular proteases with mostly unknown targets in the human proteome. To assist with bacterial protease target discovery, we have applied and compared two N-terminomics methods to investigate cleavage of human serum proteins by S. aureus V8 protease, discovering 85 host-protein targets. Among these are virulence-relevant complement, iron sequestration, clotting cascade, and host protease inhibitor proteins. Protein cleavage sites have been identified, providing insight into the disruption of host protein function by V8. Complement proteins are cleaved within peptidase and sushi domains, and host protease inhibitors are cleaved outside their protease-trapping motifs. Our data highlight the potential for further application of N-terminomics in discovery of bacterial protease substrates in other host niches and provide omics-scale insight into the role of the V8 protease in S. aureus pathogenesis.

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“…Virulence factor production in Staphylococcus aureus is largely under the control of the accessory gene regulator (agr) QS system (agrBDCA), the SaeRS and ArlRS QS systems, as well as the transcriptional regulators SarA and MgrA [308,[366][367][368][369][370] (Figure 9). There are four agr groups, all of which exhibit bacterial interference [366,370,371].…”

Section: Tcss In Staphylococcus Aureusmentioning

confidence: 99%

Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria

Sionov

Steinberg

2022

Microorganisms

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Chronic and recurrent bacterial infections are frequently associated with the formation of biofilms on biotic or abiotic materials that are composed of mono- or multi-species cultures of bacteria/fungi embedded in an extracellular matrix produced by the microorganisms. Biofilm formation is, among others, regulated by quorum sensing (QS) which is an interbacterial communication system usually composed of two-component systems (TCSs) of secreted autoinducer compounds that activate signal transduction pathways through interaction with their respective receptors. Embedded in the biofilms, the bacteria are protected from environmental stress stimuli, and they often show reduced responses to antibiotics, making it difficult to eradicate the bacterial infection. Besides reduced penetration of antibiotics through the intricate structure of the biofilms, the sessile biofilm-embedded bacteria show reduced metabolic activity making them intrinsically less sensitive to antibiotics. Moreover, they frequently express elevated levels of efflux pumps that extrude antibiotics, thereby reducing their intracellular levels. Some efflux pumps are involved in the secretion of QS compounds and biofilm-related materials, besides being important for removing toxic substances from the bacteria. Some efflux pump inhibitors (EPIs) have been shown to both prevent biofilm formation and sensitize the bacteria to antibiotics, suggesting a relationship between these processes. Additionally, QS inhibitors or quenchers may affect antibiotic susceptibility. Thus, targeting elements that regulate QS and biofilm formation might be a promising approach to combat antibiotic-resistant biofilm-related bacterial infections.

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SarA plays a predominant role in controlling the production of extracellular proteases in the diverse clinical isolates ofStaphylococcus aureusLAC and UAMS-1

Abstract: SarA plays a predominant role in controlling the production of extracellular proteases in the diverse clinical isolates of Staphylococcus aureus LAC and UAMS-1

Cited by 17 publications

References 89 publications

Screening transcriptional connections in Staphylococcus aureus using high-throughput transduction of bioluminescent reporter plasmids

Screening transcriptional connections in Staphylococcus aureus using high-throughput transduction of bioluminescent reporter plasmids

Insight into the human pathodegradome of the V8 protease from Staphylococcus aureus

Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria

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