Housefly Phormicin inhibits Staphylococcus aureus and MRSA by disrupting biofilm formation and altering gene expression in vitro and in vivo

ABSTRACT Products of the intercellular adhesion (ica) operon in Staphylococcus aureus and Staphylococcus epidermidis synthesize a linear β-1,6-linked glucosaminylglycan. This extracellular polysaccharide mediates bacterial cell-cell adhesion and is required for biofilm formation, which is thought to increase the virulence of both pathogens in association with prosthetic biomedical implants. The environmental signal(s) that triggers ica gene product and polysaccharide expression is unknown. Here we demonstrate that anaerobic in vitro growth conditions lead to increased polysaccharide expression in both S. aureus and S. epidermidis, although the regulation is less stringent inS. epidermidis. Anaerobiosis also dramatically stimulates ica-specific mRNA expression inica- and polysaccharide-positive strains of both S. aureus and S. epidermidis.These data suggest a mechanism whereby ica gene expression and polysaccharide production may act as a virulence factor in an anaerobic environment in vivo.

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Evaluation of Antibiotics Active against Methicillin-Resistant Staphylococcus aureus Based on Activity in an Established Biofilm

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01251-16 ◽

2016 ◽

Vol 60 (10) ◽

pp. 5688-5694 ◽

Cited By ~ 23

Author(s):

Daniel G. Meeker ◽

Karen E. Beenken ◽

Weston B. Mills ◽

Allister J. Loughran ◽

Horace J. Spencer ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Biofilm Formation ◽

Limit Of Detection ◽

Relative Activity ◽

Methicillin Resistant ◽

Content Type ◽

Comparable Activity ◽

Antibiotic Delivery

ABSTRACTWe usedin vitroandin vivomodels of catheter-associated biofilm formation to compare the relative activity of antibiotics effective against methicillin-resistantStaphylococcus aureus(MRSA) in the specific context of an established biofilm. The results demonstrated that, underin vitroconditions, daptomycin and ceftaroline exhibited comparable activity relative to each other and greater activity than vancomycin, telavancin, oritavancin, dalbavancin, or tigecycline. This was true when assessed using established biofilms formed by the USA300 methicillin-resistant strain LAC and the USA200 methicillin-sensitive strain UAMS-1. Oxacillin exhibited greater activity against UAMS-1 than LAC, as would be expected, since LAC is an MRSA strain. However, the activity of oxacillin was less than that of daptomycin and ceftaroline even against UAMS-1. Among the lipoglycopeptides, telavancin exhibited the greatest overall activity. Specifically, telavancin exhibited greater activity than oritavancin or dalbavancin when tested against biofilms formed by LAC and was the only lipoglycopeptide capable of reducing the number of viable bacteria below the limit of detection. With biofilms formed by UAMS-1, telavancin and dalbavancin exhibited comparable activity relative to each other and greater activity than oritavancin. Importantly, ceftaroline was the only antibiotic that exhibited greater activity than vancomycin when testedin vivoin a murine model of catheter-associated biofilm formation. These results emphasize the need to consider antibiotics other than vancomycin, most notably, ceftaroline, for the treatment of biofilm-associatedS. aureusinfections, including by the matrix-based antibiotic delivery methods often employed for local antibiotic delivery in the treatment of these infections.

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Tissue Plasminogen Activator Coating on Implant Surfaces Reduces Staphylococcus aureus Biofilm Formation

Applied and Environmental Microbiology ◽

10.1128/aem.02803-15 ◽

2015 ◽

Vol 82 (1) ◽

pp. 394-401 ◽

Cited By ~ 14

Author(s):

Jakub Kwiecinski ◽

Manli Na ◽

Anders Jarneborn ◽

Gunnar Jacobsson ◽

Marijke Peetermans ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Medical Devices ◽

Biofilm Formation ◽

Bacterial Biofilm ◽

Content Type ◽

Tissue Plasminogen

ABSTRACTStaphylococcus aureusbiofilm infections of indwelling medical devices are a major medical challenge because of their high prevalence and antibiotic resistance. As fibrin plays an important role inS. aureusbiofilm formation, we hypothesize that coating of the implant surface with fibrinolytic agents can be used as a new method of antibiofilm prophylaxis. The effect of tissue plasminogen activator (tPA) coating onS. aureusbiofilm formation was tested within vitromicroplate biofilm assays and anin vivomouse model of biofilm infection. tPA coating efficiently inhibited biofilm formation by variousS. aureusstrains. The effect was dependent on plasminogen activation by tPA, leading to subsequent local fibrin cleavage. A tPA coating on implant surfaces prevented both early adhesion and later biomass accumulation. Furthermore, tPA coating increased the susceptibility of biofilm infections to antibiotics.In vivo, significantly fewer bacteria were detected on the surfaces of implants coated with tPA than on control implants from mice treated with cloxacillin. Fibrinolytic coatings (e.g., with tPA) reduceS. aureusbiofilm formation bothin vitroandin vivo, suggesting a novel way to prevent bacterial biofilm infections of indwelling medical devices.

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18β-Glycyrrhetinic Acid Inhibits Methicillin-Resistant Staphylococcus aureus Survival and Attenuates Virulence Gene Expression

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01023-12 ◽

2012 ◽

Vol 57 (1) ◽

pp. 241-247 ◽

Cited By ~ 32

Author(s):

Danyelle R. Long ◽

Julia Mead ◽

Jay M. Hendricks ◽

Michele E. Hardy ◽

Jovanka M. Voyich

Keyword(s):

Gene Expression ◽

Staphylococcus Aureus ◽

Virulence Gene ◽

Glycyrrhetinic Acid ◽

Licorice Root ◽

Methicillin Resistant ◽

Content Type ◽

Virulence Gene Expression

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) has become a major source of infection in hospitals and in the community. Increasing antibiotic resistance inS. aureusstrains has created a need for alternative therapies to treat disease. A component of the licorice rootGlycyrrhizaspp., 18β-glycyrrhetinic acid (GRA), has been shown to have antiviral, antitumor, and antibacterial activity. This investigation explores thein vitroandin vivoeffects of GRA on MRSA pulsed-field gel electrophoresis (PFGE) type USA300. GRA exhibited bactericidal activity at concentrations exceeding 0.223 μM. Upon exposure ofS. aureusto sublytic concentrations of GRA, we observed a reduction in expression of key virulence genes, includingsaeRandhla. In murine models of skin and soft tissue infection, topical GRA treatment significantly reduced skin lesion size and decreased the expression ofsaeRandhlagenes. Our investigation demonstrates that at high concentrations GRA is bactericidal to MRSA and at sublethal doses it reduces virulence gene expression inS. aureusbothin vitroandin vivo.

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Oral Administration of the Broad-Spectrum Antibiofilm Compound Toremifene Inhibits Candida albicans and Staphylococcus aureus Biofilm FormationIn Vivo

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03869-14 ◽

2014 ◽

Vol 58 (12) ◽

pp. 7606-7610 ◽

Cited By ~ 16

Author(s):

Kaat De Cremer ◽

Nicolas Delattin ◽

Katrijn De Brucker ◽

Annelies Peeters ◽

Soña Kucharíková ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Candida Albicans ◽

Broad Spectrum ◽

Staphylococcus Epidermidis ◽

Biofilm Formation ◽

Candida Krusei ◽

Content Type ◽

And Staphylococcus Aureus

ABSTRACTWe here report on thein vitroactivity of toremifene to inhibit biofilm formation of different fungal and bacterial pathogens, includingCandida albicans,Candida glabrata,Candida dubliniensis,Candida krusei,Pseudomonas aeruginosa,Staphylococcus aureus, andStaphylococcus epidermidis. We validated thein vivoefficacy of orally administered toremifene againstC. albicans and S. aureusbiofilm formation in a rat subcutaneous catheter model. Combined, our results demonstrate the potential of toremifene as a broad-spectrum oral antibiofilm compound.

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Biosurfactants of Lactobacillus helveticus for biodiversity inhibit the biofilm formation of Staphylococcus aureus and cell invasion

Future Microbiology ◽

10.2217/fmb-2018-0354 ◽

2019 ◽

Vol 14 (13) ◽

pp. 1133-1146 ◽

Cited By ~ 3

Author(s):

Xinpeng Jiang ◽

Xin Yan ◽

Shanshan Gu ◽

Yan Yang ◽

Lili Zhao ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Host Cell ◽

Biofilm Formation ◽

Lactobacillus Helveticus ◽

Real Time Quantitative Pcr ◽

Autoinducer 2 ◽

New Strategy ◽

Better Than

Aim: This study aimed to evaluate the differences of biosurfactants produced by two Lactobacillus helveticus strains against the biofilm formation of Staphylococcus aureus in vitro and in vivo. Materials & methods: Scanning electron microscopy, Real time-quantitative PCR (RT-qPCR) and cell assay were used to analyze the inhibiting effect of biosurfactants against biofilm formation. Results & conclusion: Results showed that the biosurfactants have anti-adhesive and inhibiting effects on biofilm formation in vivo and in vitro. The biofilm-formative genes and autoinducer-2 signaling regulated these characteristics, and the biosurfactant L. helveticus 27170 is better than that of 27058. Host cell adhesion and invasion results indicated that the biosurfactants L. helveticus prevented the S. aureus invading the host cell, which may be a new strategy to eliminate biofilms.

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Carvacrol Targets SarA and CrtM of Methicillin-Resistant Staphylococcus aureus to Mitigate Biofilm Formation and Staphyloxanthin Synthesis: An In Vitro and In Vivo Approach

ACS Omega ◽

10.1021/acsomega.0c04252 ◽

2020 ◽

Vol 5 (48) ◽

pp. 31100-31114

Author(s):

Anthonymuthu Selvaraj ◽

Alaguvel Valliammai ◽

Pandiyan Muthuramalingam ◽

Arumugam Priya ◽

Manokaran Suba ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Biofilm Formation ◽

Methicillin Resistant Staphylococcus Aureus ◽

Methicillin Resistant

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The Impacts of msaABCR on sarA-Associated Phenotypes Are Different in Divergent Clinical Isolates of Staphylococcus aureus

Infection and Immunity ◽

10.1128/iai.00530-19 ◽

2019 ◽

Vol 88 (2) ◽

Author(s):

Joseph S. Rom ◽

Aura M. Ramirez ◽

Karen E. Beenken ◽

Gyan S. Sahukhal ◽

Mohamed O. Elasri ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Biofilm Formation ◽

Clinical Isolates ◽

Protease Production ◽

Relative Impact ◽

Extracellular Proteases ◽

Content Type ◽

The Impact

ABSTRACT The staphylococcal accessory regulator (sarA) plays an important role in Staphylococcus aureus infections, including osteomyelitis, and the msaABCR operon has been implicated as an important factor in modulating expression of sarA. Thus, we investigated the contribution of msaABCR to sarA-associated phenotypes in the S. aureus clinical isolates LAC and UAMS-1. Mutation of msaABCR resulted in reduced production of SarA and a reduced capacity to form a biofilm in both strains. Biofilm formation was enhanced in a LAC msa mutant by restoring the production of SarA, but this was not true in a UAMS-1 msa mutant. Similarly, extracellular protease production was increased in a LAC msa mutant but not a UAMS-1 msa mutant. This difference was reflected in the accumulation and distribution of secreted virulence factors and in the impact of extracellular proteases on biofilm formation in a LAC msa mutant. Most importantly, it was reflected in the relative impact of mutating msa as assessed in a murine osteomyelitis model, which had a significant impact in LAC but not in UAMS-1. In contrast, mutation of sarA had a greater impact on all of these in vitro and in vivo phenotypes than mutation of msaABCR, and it did so in both LAC and UAMS-1. These results suggest that, at least in osteomyelitis, it would be therapeutically preferable to target sarA rather than msaABCR to achieve the desired clinical result, particularly in the context of divergent clinical isolates of S. aureus.

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NorB, an Efflux Pump in Staphylococcus aureus Strain MW2, Contributes to Bacterial Fitness in Abscesses

Journal of Bacteriology ◽

10.1128/jb.00655-08 ◽

2008 ◽

Vol 190 (21) ◽

pp. 7123-7129 ◽

Cited By ~ 89

Author(s):

Yanpeng Ding ◽

Yoshikuni Onodera ◽

Jean C. Lee ◽

David C. Hooper

Keyword(s):

Gene Expression ◽

Staphylococcus Aureus ◽

Efflux Pump ◽

Efflux Pumps ◽

Single Copy ◽

Aureus Strain ◽

Bacterial Survival ◽

Bacterial Fitness

ABSTRACT While remaining a major problem in hospitals, Staphylococcus aureus is now spreading in communities. Strain MW2 (USA400 lineage) and other community methicillin-resistant S. aureus strains most commonly cause skin infections with abscess formation. Multidrug resistance (MDR) efflux pumps contribute to antimicrobial resistance but may also contribute to bacterial survival by removal of environmental toxins. In S. aureus, NorA, NorB, NorC, and Tet38 are chromosomally encoded efflux pumps whose overexpression can confer MDR to quinolones and other compounds (Nor pumps) or tetracyclines alone (Tet38), but the natural substrates of these pumps are not known. To determine the role of these efflux pumps in a natural environment in the absence of antibiotics, we used strain MW2 in a mouse subcutaneous abscess model and compared pump gene expression as determined by reverse transcription-PCR in the abscesses and in vitro. norB and tet38 were selectively upregulated in vivo more than 171- and 24-fold, respectively, whereas norA and norC were downregulated. These changes were associated with an increase in expression of mgrA, which encodes a transcriptional regulator known to affect pump gene expression. In competition experiments using equal inocula of a norB or tet38 mutant and parent strain MW2, each mutant exhibited growth defects of about two- to threefold in vivo. In complementation experiments, a single-copy insertion of norB (but not a single-copy insertion of tet38) in the attB site within geh restored the growth fitness of the norB mutant in vivo. Our findings indicate that some MDR pumps, like NorB, can facilitate bacterial survival when they are overexpressed in a staphylococcal abscess and may contribute to the relative resistance of abscesses to antimicrobial therapy, thus linking bacterial fitness and resistance in vivo.

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