Minocycline versus doxycycline for meticillin-resistant Staphylococcus aureus (MRSA): in vitro susceptibility versus in vivo effectiveness

ABSTRACT The DltABCD and MprF proteins contribute a net positive charge to the Staphylococcus aureus surface envelope by alanylating and lysinylating teichoic acids and membrane phosphatidylglycerol, respectively. These surface charge modifications are associated with increased in vitro resistance profiles of S. aureus to a number of endogenous cationic antimicrobial peptides (CAPs), such as α-defensins. The current study investigated the effects of dltA and mprF mutations on the following host factors relevant to endovascular infections: (i) in vitro susceptibility to the CAP thrombin-induced platelet microbicidal protein 1 (tPMP-1), (ii) in vitro adherence to endothelial cells (EC) and matrix proteins, and (iii) in vivo virulence in an endovascular infection model (rabbit endocarditis) in which tPMP-1 is felt to play a role in limiting S. aureus pathogenesis. Both mutations resulted in substantial increases in the in vitro susceptibility to tPMP-1 compared to that of the parental strain. The dltA (but not the mprF) mutation resulted in a significantly reduced capacity to bind to EC in vitro, while neither mutation adversely impacted in vitro binding to fibronectin, fibrinogen, or platelets. In vivo, both mutations significantly attenuated virulence in terms of early colonization of sterile vegetations and subsequent proliferation at this site (versus the parental strain). However, only the dltA mutation significantly reduced metastatic infections in kidneys and spleens compared to those in animals infected with the parental strain. These data underscore the importance of resistance to distinct CAPs and of teichoic acid-dependent EC interactions in the context of endovascular infection pathogenesis.

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Inducible and constitutive clindamycin resistance in Staphylococcus aureus in a northeastern Indian tertiary care hospital

The Journal of Infection in Developing Countries ◽

10.3855/jidc.6336 ◽

2015 ◽

Vol 9 (07) ◽

pp. 725-731 ◽

Cited By ~ 1

Author(s):

Amit Banik ◽

Annie Bakorlin Khyriem ◽

Jeetendra Gurung ◽

Valarie Wihiwot Lyngdoh

Keyword(s):

Staphylococcus Aureus ◽

Care Center ◽

Treatment Options ◽

Tertiary Care ◽

Care Hospital ◽

Sensitivity Testing ◽

In Vitro Susceptibility ◽

Routine Identification

Introduction: Staphylococcus aureus is one of the most common pyogenic bacteria. They are notorious for developing prompt resistance to newer antimicrobials. With increasing incidence of methicillin-resistant S. aureus (MRSA) isolates, the treatment options are also becoming limited. Clindamycin is an excellent drug for skin and soft tissue infections, but resistance mediated by the inducible phenotype (iMLSB) leads to in vivo therapeutic failure even though there may be in vitro susceptibility. The double disk approximation test (D-test) can reliably detect the presence of such isolates. This study was aimed to detect and report the prevalence of the iMLSB phenotype in NEIGRIHMS, a tertiary care center in Northeast India. Methodology: A total of 243 consecutive isolates were subjected to routine identification tests followed by antimicrobial sensitivity testing. Erythromycin-resistant isolates were tested for inducible resistance phenotype by the D-test. Results: Among strains tested, 95 (39%) were erythromycin resistant. Twenty-six (10.7%) isolates were D-test positive (iMLSB phenotype), 41 (16.88%) were constitutively resistant (cMLSB phenotype), and 28 isolates (11.52%) were found to be negative by D-test. The incidence of both inducible and constitutive phenotypes was higher in MRSA isolates compared to methicillin-sensitive S. aureus (MSSA) isolates. Conclusions: This study revealed a moderate prevalence of the inducible clindamycin phenotype in the staphylococcal isolates tested. Clinical microbiology laboratories in areas of high MRSA prevalence should consider performing the D-test routinely. This will help prevent prescription of drug(s) whose therapeutic efficacy is doubtful.

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Metabolic interventions for the prevention and treatment of daptomycin non-susceptibility in Staphylococcus aureus

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkz194 ◽

2019 ◽

Vol 74 (8) ◽

pp. 2274-2283 ◽

Cited By ~ 4

Author(s):

Joseph M Reed ◽

Stewart G Gardner ◽

Nagendra N Mishra ◽

Arnold S Bayer ◽

Greg A Somerville

Keyword(s):

Staphylococcus Aureus ◽

Metabolic Pathways ◽

Tricarboxylic Acid Cycle ◽

Metabolic Inhibitors ◽

In Vitro Susceptibility ◽

Metabolic Adaptations ◽

Essential Enzyme ◽

Emergence Of Resistance

AbstractBackgroundA major developing problem in the treatment of Staphylococcus aureus infections is the emergence of resistance during treatment with daptomycin. Previous metabolomic analyses of isogenic S. aureus strains prior to and after evolution into a daptomycin non-susceptible (DapNS) state provided important metabolic information about this transition (e.g. perturbations of the tricarboxylic acid cycle).ObjectivesTo assess the significance of these metabolic changes, in vitro susceptibility to daptomycin was determined in daptomycin-susceptible (DapS) and DapNSS. aureus strains cultivated with metabolic inhibitors targeting these changes.MethodsOnly inhibitors that are approved for use in humans were chosen (i.e. fosfomycin, valproate, trimetazidine and 6-mercaptopurine) to assess the importance of metabolic pathways for daptomycin non-susceptibility. The ability of these inhibitors to forestall the emergence of DapNS strains was also assessed.ResultsThe combination of daptomycin and fosfomycin synergistically killed both DapS and DapNS strains in vitro and enhanced the in vivo outcome against a DapNS strain in experimental endocarditis. Interestingly, fosfomycin acts on the peptidoglycan biosynthetic enzyme UDP-N-acetylglucosamine enolpyruvyl transferase (MurA); however, it also had a significant effect on the enzymatic activity of enolase, an essential enzyme in S. aureus. While fosfomycin acted synergistically with daptomycin, it failed to prevent the in vitro evolution of daptomycin non-susceptibility. In contrast, trimetazidine, an anti-angina drug that stimulates glucose oxidation, abolished the ability of DapSS. aureus strains to transition to a DapNS state.ConclusionsThese data reveal that metabolic adaptations associated with DapNS strains can be targeted to prevent the emergence of and/or reverse pre-existing resistance to daptomycin.

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Faculty Opinions recommendation of Decreasing in vitro susceptibility of clinical Staphylococcus aureus isolates to vancomycin at the New York Hospital: quantitative testing redux.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13485031.14862158 ◽

2012 ◽

Author(s):

George Sakoulas

Keyword(s):

New York ◽

Staphylococcus Aureus ◽

In Vitro Susceptibility ◽

York Hospital

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In vitro susceptibility of T lymphocytes from chimpanzees (Pan troglodytes) to human herpesvirus 6 (HHV-6): a potential animal model to study the interaction between HHV-6 and human immunodeficiency virus type 1 in vivo.

Journal of Virology ◽

10.1128/jvi.64.6.2751-2758.1990 ◽

1990 ◽

Vol 64 (6) ◽

pp. 2751-2758 ◽

Cited By ~ 26

Author(s):

P Lusso ◽

P D Markham ◽

S E DeRocco ◽

R C Gallo

Keyword(s):

Human Immunodeficiency Virus ◽

Animal Model ◽

Pan Troglodytes ◽

Human Herpesvirus ◽

Human Herpesvirus 6 ◽

In Vitro Susceptibility ◽

Immunodeficiency Virus

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Cu(II) coordination polymer: treatment effect on catheter-associated urinary tract infectious via suppressing Staphylococcus aureus growth in vitro and in vivo

Inorganic and Nano-Metal Chemistry ◽

10.1080/24701556.2020.1835970 ◽

2020 ◽

pp. 1-5

Author(s):

Zhi-Wang Tang ◽

Xu-Zhong Liu ◽

Ai-Di Ma ◽

Lu Ji

Keyword(s):

Staphylococcus Aureus ◽

Urinary Tract ◽

Coordination Polymer ◽

Treatment Effect

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Group V Phospholipase A2 Mediates Endothelial Dysfunction and Acute Lung Injury Caused by Methicillin-Resistant Staphylococcus aureus

Cells ◽

10.3390/cells10071731 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1731

Author(s):

Yu Maw Htwe ◽

Huashan Wang ◽

Patrick Belvitch ◽

Lucille Meliton ◽

Mounica Bandela ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Acute Lung Injury ◽

Endothelial Dysfunction ◽

Lung Injury ◽

Phospholipase A2 ◽

Methicillin Resistant Staphylococcus Aureus ◽

Group V ◽

Methicillin Resistant

Lung endothelial dysfunction is a key feature of acute lung injury (ALI) and clinical acute respiratory distress syndrome (ARDS). Previous studies have identified the lipid-generating enzyme, group V phospholipase A2 (gVPLA2), as a mediator of lung endothelial barrier disruption and inflammation. The current study aimed to determine the role of gVPLA2 in mediating lung endothelial responses to methicillin-resistant Staphylococcus aureus (MRSA, USA300 strain), a major cause of ALI/ARDS. In vitro studies assessed the effects of gVPLA2 inhibition on lung endothelial cell (EC) permeability after exposure to heat-killed (HK) MRSA. In vivo studies assessed the effects of intratracheal live or HK-MRSA on multiple indices of ALI in wild-type (WT) and gVPLA2-deficient (KO) mice. In vitro, HK-MRSA increased gVPLA2 expression and permeability in human lung EC. Inhibition of gVPLA2 with either the PLA2 inhibitor, LY311727, or with a specific monoclonal antibody, attenuated the barrier disruption caused by HK-MRSA. LY311727 also reduced HK-MRSA-induced permeability in mouse lung EC isolated from WT but not gVPLA2-KO mice. In vivo, live MRSA caused significantly less ALI in gVPLA2 KO mice compared to WT, findings confirmed by intravital microscopy assessment in HK-MRSA-treated mice. After targeted delivery of gVPLA2 plasmid to lung endothelium using ACE antibody-conjugated liposomes, MRSA-induced ALI was significantly increased in gVPLA2-KO mice, indicating that lung endothelial expression of gVPLA2 is critical in vivo. In summary, these results demonstrate an important role for gVPLA2 in mediating MRSA-induced lung EC permeability and ALI. Thus, gVPLA2 may represent a novel therapeutic target in ALI/ARDS caused by bacterial infection.

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In Vitro Antibacterial Effect of the Methanolic Extract of the Korean Soybean Fermented Product Doenjang against Staphylococcus aureus

Animals ◽

10.3390/ani11082319 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2319

Author(s):

Klara Lalouckova ◽

Lucie Mala ◽

Petr Marsik ◽

Eva Skrivanova

Keyword(s):

Staphylococcus Aureus ◽

High Performance ◽

Methanolic Extract ◽

Bioactive Substances ◽

Microdilution Method ◽

Antibacterial Compound ◽

Fermented Product ◽

Broth Microdilution Method

Ultra-high performance liquid chromatography/mass spectrometry showed soyasaponin I and the isoflavones daidzein, genistein, and glycitein to be the main components of the methanolic extract of the Korean soybean fermented product doenjang, which is known to be a rich source of naturally occurring bioactive substances, at average contents of 515.40, 236.30, 131.23, and 29.00 ng/mg, respectively. The antimicrobial activity of the methanolic extract of doenjang against nine Staphylococcusaureus strains was determined in vitro by the broth microdilution method to investigate its potential to serve as an alternative antibacterial compound. The results suggest that the extract is an effective antistaphylococcal agent at concentrations of 2048–4096 µg/mL. Moreover, the tested extract also showed the ability to inhibit the growth of both methicillin-sensitive and methicillin-resistant animal and clinical S. aureus isolates. The growth kinetics of the chosen strains of S. aureus at the minimum inhibitory concentration of the methanolic extract of doenjang support the idea that the tested extract acts as an antibacterial compound. To the best of our knowledge, this is the first report on the antistaphylococcal action of the methanolic extract of doenjang thus, additional studies including in vivo testing are necessary to confirm this hypothesis.

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