High and low virulence Staphylococcus aureus strains in a rabbit skin infection model

2007 ◽  
Vol 125 (3-4) ◽  
pp. 333-340 ◽  
Author(s):  
L. Meulemans ◽  
K. Hermans ◽  
L. Duchateau ◽  
F. Haesebrouck
Keyword(s):  
Staphylococcus Aureus ◽  
Skin Infection ◽  
Infection Model ◽  
Rabbit Skin

scholarly journals Insights into the Staphylococcus aureus-Host Interface: Global Changes in Host and Pathogen Gene Expression in a Rabbit Skin Infection Model

PLoS ONE ◽  
2015 ◽  
Vol 10 (2) ◽  
pp. e0117713 ◽  
Author(s):  
Natalia Malachowa ◽  
Scott D. Kobayashi ◽  
Daniel E. Sturdevant ◽  
Dana P. Scott ◽  
Frank R. DeLeo
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Skin Infection ◽  
Infection Model ◽  
Global Changes ◽  
Rabbit Skin

scholarly journals Gene expression in Staphylococcus aureus skin infection

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Marco Palma
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Mouse Model ◽  
Skin Infection ◽  
Rabbit Model ◽  
Infection Model ◽  
Hypothetical Proteins ◽  
Rabbit Skin ◽  
Genes Encoding ◽  
Mouse System

Gene expression in Staphylococcus aureus changes during infection to survive its host. Therefore, to find new strategies to combat staphylococcal infections, it is important to understand the mechanisms that this pathogen uses to adapt to its host and how the host responds to the presence of staphylococcal cells. We have reviewed two studies of gene expression in Staphylococcus aureus during skin infections, one study using a rabbit skin infection model and the other study using a diabetic skin infection model in mice. We compared the two gene expression profiles to find similarities and differences. Many genes did not show any differences in gene expression in S. aureus during the skin infection compared to the control groups. However,19 genes were upregulated in both systems include chaperones (e.g., groES, groEL, grpE, dnaK9), sodM, hrcA, sbi, and the gene encoding a cadmium-exporting ATPase protein. Also, four genes were downregulated in both systems including a gene that encodes a hydrolase and three genes for hypothetical proteins. Also, there was a group of genes expressed in different ways in the two systems. The gene expression of sarU, transcriptional regulators of the LysR family, Cro family, crp family, TetR family, tenA, and many hypothetical proteins were upregulated in the rabbit system but downregulated in the mouse system. The genes rps, rpl, rpm, and several others involved, for example, in translation and transcription were downregulated in the rabbit system but upregulated in the mouse system. Many genes that showed significant changes in overall gene expression in the rabbit model were unaffected in the mouse model. For example, in the rabbit skin infection model increased important gene regulators like agr and sarV, while some stress-response genes (e.g., sigB and lexA) were downregulated. The gene expression of several staphylococcal genes encoding virulence factors such as fibronectin-binding proteins, hemolysins, coagulases, complement inhibitory proteins, Emp, and many exotoxins were upregulated while clumping factor A was downregulated. Besides, some genes showed expression changes in the mouse model, but not in the rabbit model. For example, sarA, rot, ecb, ctsR, spx, many ribosomal proteins, and hypothetical proteins increased, while cap5k, lysE, rusA, and many hypothetical proteins decreased in the mouse model but they were unaffected in the rabbit model. On the other hand, the host responded to the S. aureus infection by inducing the expression of genes encoding host inflammatory cytokines, receptors, genes associated with neutrophil adhesion and migration, inflammation, and immune cell trafficking. In conclusion, the level of gene expression changed both in the pathogen and the host during the skin infection. The information of gene expression can make significant contributions to understand which genes are involved in the infection process, which can be targeted for antimicrobial chemotherapy.

scholarly journals Biofilm/Persister/Stationary Phase Bacteria Cause More Severe Disease Than Log Phase Bacteria – II Infection with Persister Forms of Staphylococcus aureus Causes a Chronic Persistent Skin Infection with More Severe Lesion that Takes Longer to Heal and is not Eradicated by the Current Recommended Treatment in Mice

2018 ◽  
Author(s):  
Rebecca Yee ◽  
Yuting Yuan ◽  
Cory Brayton ◽  
Andreina Tarff Leal ◽  
Jie Feng ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Stationary Phase ◽  
Skin Infection ◽  
Bacterial Load ◽  
Mouse Skin ◽  
Infection Model ◽  
Persister Cells ◽  
Persistent Infections ◽  
Recommended Treatment ◽  
Biofilm Bacteria

AbstractStaphylococcus aureus is an opportunistic pathogen that can cause persistent infections clinically. Treatment for chronic S. aureus infections ranges from at least one week to several months and such infections are prone to relapse likely due to the presence of persistent forms of bacteria such as persister cells. Persister cells, which are bacterial cells that become dormant under stress conditions, can be isolated in vitro but their clinical significance in in vivo infections are largely unclear. Here, we evaluated S. aureus persistent forms using stationary phase cultures and biofilm bacteria (enriched in persisters) in comparison with log phase cultures in terms of their ability to cause disease in a mouse skin infection model. Surprisingly, we found that infection of mice with stationary phase cultures and biofilm bacteria produced a more severe chronic skin infection with more pronounced lesions which took longer to heal than log phase (actively growing) cultures. After two week infection, the bacterial load and skin tissue pathology, as determined by hyperplasia, immune cell infiltration, and crust/lesion formation, of mice infected with the more persistent forms (e.g. stationary phase bacteria and biofilm bacteria) were greater than mice infected with log phase bacteria. Using our persistent infection mouse model, we showed that the clinically recommended treatment for recurrent S. aureus skin infection, doxycycline + rifampin, was not effective in eradicating the bacteria in the treatment study, despite reducing lesion sizes and pathology in infected mice. Analogous findings were also observed in a Caenorhabditis elegans model, where S.aureus stationary phase cultures caused a greater mortality than log phase culture as early as two days post-infection. Thus, we established a new model for chronic persistent infections using persister bacteria that could serve as a relevant model to evaluate therapeutic options for persistent infections in general. Our findings connect persisters with persistent infections, have implications for understanding disease pathogenesis, and are likely to be broadly valid for other pathogens.

scholarly journals Improved Oxacillin Treatment Outcomes in Experimental Skin and Lung Infection by a Methicillin-Resistant Staphylococcus aureus Isolate with avraSROperon Deletion

2011 ◽  
Vol 55 (6) ◽  
pp. 2818-2823 ◽  
Author(s):  
Dae Sun Jo ◽  
Christopher P. Montgomery ◽  
Shaohui Yin ◽  
Susan Boyle-Vavra ◽  
Robert S. Daum
Keyword(s):  
Staphylococcus Aureus ◽  
Mutant Strain ◽  
Skin Infection ◽  
Soft Tissues ◽  
Infection Model ◽  
Necrotizing Pneumonia ◽  
Bacterial Burden ◽  
Methicillin Resistant ◽  
Content Type ◽  
Oxacillin Resistance

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) strains are major pathogens causing infections of the skin and soft tissues and more serious, life-threatening diseases, including sepsis and necrotizing pneumonia. ThevraSRoperon encodes the key regulatory system that modulates the stress response ofS. aureuselicited upon exposure to cell wall antibiotics. Mutation ofvraSandvraRresults in decreased oxacillin resistancein vitro. We investigated the effect of oxacillin treatment in experimental models employing a clinical USA300 MRSA strain (strain 923) and an isogenicvraSRdeletion mutant (strain 923-M23). In a murine model ofS. aureusnecrotizing pneumonia, animals were treated with oxacillin, beginning 15 min after inoculation. Among mice infected with mutant strain 923-M23, oxacillin treatment significantly improved survival compared with saline treatment, whereas oxacillin treatment had no effect in mice infected with strain 923. Similarly, treatment with oxacillin decreased the bacterial burden among animals infected with strain 923-M23 but not among animals infected with strain 923. In a murine skin infection model, oxacillin eliminated the development of dermonecrosis among 923-M23-infected mice and decreased the bacterial burden in the lesions, but not among strain 923-infected mice. We conclude that deletion of thevraSRoperon allowed an oxacillin regimen to be effective in murine models of MRSA pneumonia and skin infection. These findings provide proof-of-principle for development of a new antibiotic that could restore the usefulness of oxacillin against MRSA by inhibiting VraS or VraR.

scholarly journals Efficacy of a New Fluoroquinolone, JNJ-Q2, in Murine Models of Staphylococcus aureus and Streptococcus pneumoniae Skin, Respiratory, and Systemic Infections

2011 ◽  
Vol 55 (12) ◽  
pp. 5522-5528 ◽  
Author(s):  
Jeffrey Fernandez ◽  
Jamese J. Hilliard ◽  
Brian J. Morrow ◽  
John L. Melton ◽  
Robert K. Flamm ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Tract Infection ◽  
Lower Respiratory Tract ◽  
Skin Infection ◽  
Infection Model ◽  
Content Type ◽  
Infection Models ◽  
Resistant Mutants ◽  
Selection Of

ABSTRACTThein vivoefficacy of JNJ-Q2, a new broad-spectrum fluoroquinolone (FQ), was evaluated in a murine septicemia model with methicillin-susceptibleStaphylococcus aureus(MSSA) and methicillin-resistantS. aureus(MRSA) and in aStreptococcus pneumoniaelower respiratory tract infection model. JNJ-Q2 and comparators were also evaluated in an acute murine skin infection model using a community-acquired MRSA strain and in an established skin infection (ESI) model using a hospital-acquired strain, for which the selection of resistant mutants was also determined. JNJ-Q2 demonstrated activity in the MSSA septicemia model that was comparable to that moxifloxacin (JNJ-Q2 50% effective dose [ED50], 0.2 mg/kg of body weight administered subcutaneously [s.c.] and 2 mg/kg administered orally [p.o.]) and activity in the MRSA septicemia model that was superior to that of vancomycin (JNJ-Q2 ED50, 1.6 mg/kg administered s.c.). In anS. pneumoniaelower respiratory tract infection model, JNJ-Q2 displayed activity (ED50, 1.9 mg/kg administered s.c. and 7.4 mg/kg administered p.o.) that was comparable to that of gemifloxacin and superior to that of moxifloxacin. In both MRSA skin infection models, treatment with JNJ-Q2 resulted in dose-dependent reductions in bacterial titers in the skin, with the response to JNJ-Q2 at each dose exceeding the responses of the comparators ciprofloxacin, moxifloxacin, linezolid, and vancomycin. Additionally, in the ESI model, JNJ-Q2 showed a low or nondetectable propensity for ciprofloxacin resistance selection, in contrast to the selection of ciprofloxacin-resistant mutants observed for both ciprofloxacin and moxifloxacin. JNJ-Q2 demonstrated activity that was comparable or superior to the activity of fluoroquinolone or antistaphylococcal comparators in several local and systemic skin infection models performed with bothS. aureusandS. pneumoniaeand is currently being evaluated in phase II human clinical trials.

scholarly journals Cefazolin and Ertapenem, a Synergistic Combination Used To Clear Persistent Staphylococcus aureus Bacteremia

2016 ◽  
Vol 60 (11) ◽  
pp. 6609-6618 ◽  
Author(s):  
George Sakoulas ◽  
Joshua Olson ◽  
Juwon Yim ◽  
Niedita B. Singh ◽  
Monika Kumaraswamy ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Skin Infection ◽  
Disk Diffusion ◽  
Pharmacodynamic Modeling ◽  
Infection Model ◽  
Content Type ◽  
Bloodstream Isolate ◽  
Drug Concentrations

ABSTRACTErtapenem and cefazolin were used in combination to successfully clear refractory methicillin-susceptibleStaphylococcus aureus(MSSA) bacteremia. In addition, recent work has demonstrated activity of combination therapy with beta-lactams from different classes against methicillin-resistantS. aureus(MRSA). The ertapenem-plus-cefazolin combination was evaluated for synergyin vitroandin vivoin a murine skin infection model using an index MSSA bloodstream isolate from a patient in whom persistent bacteremia was cleared with this combination and against a cadre of well-described research strains and clinical strains of MSSA and MRSA. Against the index MSSA bloodstream isolate, ertapenem and cefazolin showed synergy using both checkerboard (fractional inhibitory concentration [FIC] index = 0.375) and time-kill assays. Using a disk diffusion ertapenem potentiation assay, the MSSA isolate showed a cefazolin disk zone increased from 34 to 40 mm.In vitropharmacokinetic/pharmacodynamic modeling at clinically relevant drug concentrations demonstrated bactericidal activity (>3 log10-CFU/ml reduction) of the combination but bacteriostatic activity of ether drug alone at 48 h. A disk diffusion potentiation assay showed that ertapenem increased the cefazolin zone of inhibition by >3 mm for 34/35 (97%) MSSA and 10/15 (67%) MRSA strains. A murine skin infection model of MSSA showed enhanced activity of cefazolin plus ertapenem compared to monotherapy with these agents. After successful use in clearance of MSSA bacteremia, the combination of ertapenem and cefazolin showed synergy against MSSAin vitroandin vivo. This combination may warrant consideration for future clinical study in MSSA bacteremia.

scholarly journals Galectin-3 Is a Target for Proteases Involved in the Virulence of Staphylococcus aureus

2017 ◽  
Vol 85 (7) ◽  
Author(s):  
Jonas Elmwall ◽  
Jakub Kwiecinski ◽  
Manli Na ◽  
Abukar Ahmed Ali ◽  
Veronica Osla ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Skin Infection ◽  
Bacterial Load ◽  
Lesion Size ◽  
Human Neutrophils ◽  
Infection Model ◽  
Content Type ◽  
Immune Evasion Mechanism ◽  
Galectin 3 ◽  
The Impact

ABSTRACT Staphylococcus aureus is a major cause of skin and soft tissue infection. The bacterium expresses four major proteases that are emerging as virulence factors: aureolysin (Aur), V8 protease (SspA), staphopain A (ScpA), and staphopain B (SspB). We hypothesized that human galectin-3, a β-galactoside-binding lectin involved in immune regulation and antimicrobial defense, is a target for these proteases and that proteolysis of galectin-3 is a novel immune evasion mechanism. Indeed, supernatants from laboratory strains and clinical isolates of S. aureus caused galectin-3 degradation. Similar proteolytic capacities were found in Staphylococcus epidermidis isolates but not in Staphylococcus saprophyticus. Galectin-3-induced activation of the neutrophil NADPH oxidase was abrogated by bacterium-derived proteolysis of galectin-3, and SspB was identified as the major protease responsible. The impact of galectin-3 and protease expression on S. aureus virulence was studied in a murine skin infection model. In galectin-3+/+ mice, SspB-expressing S. aureus caused larger lesions and resulted in higher bacterial loads than protease-lacking bacteria. No such difference in bacterial load or lesion size was detected in galectin-3−/− mice, which overall showed smaller lesion sizes than the galectin-3+/+ animals. In conclusion, the staphylococcal protease SspB inactivates galectin-3, abrogating its stimulation of oxygen radical production in human neutrophils and increasing tissue damage during skin infection.

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