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 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

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 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 Efflux-Related Resistance to Norfloxacin, Dyes, and Biocides in Bloodstream Isolates of Staphylococcus aureus

2007 ◽  
Vol 51 (9) ◽  
pp. 3235-3239 ◽  
Author(s):  
Carmen E. DeMarco ◽  
Laurel A. Cushing ◽  
Emmanuel Frempong-Manso ◽  
Susan M. Seo ◽  
Tinevimbo A. A. Jaravaza ◽  
...  
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Efflux Pump Inhibitor ◽  
Qrt Pcr ◽  
Reverse Transcription Pcr ◽  
Environmental Surfaces ◽  
Genes Encoding ◽  
High Level

ABSTRACT Efflux is an important resistance mechanism in Staphylococcus aureus, but its frequency in patients with bacteremia is unknown. Nonreplicate bloodstream isolates were collected over an 8-month period, and MICs of four common efflux pump substrates, with and without the broad-spectrum efflux pump inhibitor reserpine, were determined (n = 232). A reserpine-associated fourfold decrease in MIC was considered indicative of efflux. Strains exhibiting efflux of at least two of the four substrates were identified (“effluxing strains” [n = 114]). For these strains, MICs with or without reserpine for an array of typical substrates and the expression of mepA, mdeA, norA, norB, norC, and qacA/B were determined using quantitative real-time reverse transcription-PCR (qRT-PCR). A fourfold or greater increase in gene expression was considered significant. The most commonly effluxed substrates were ethidium bromide and chlorhexidine (100 and 96% of effluxing strains, respectively). qRT-PCR identified strains overexpressing mepA (5 [4.4%]), mdeA (13 [11.4%]), norA (26 [22.8%]), norB (29 [25.4%]), and norC (19 [16.7%]); 23 strains overexpressed two or more genes. Mutations probably associated with increased gene expression included a MepR-inactivating substitution and norA promoter region insertions or deletions. Mutations possibly associated with increased expression of the other analyzed genes were also observed. Effluxing strains comprised 49% of all strains studied (114/232 strains), with nearly half of these overexpressing genes encoding MepA, MdeA, and/or NorABC (54/114 strains). Reduced susceptibility to biocides may contribute to persistence on environmental surfaces, and efflux of drugs such as fluoroquinolones may predispose strains to high-level target-based resistance.

Mouse Model of Staphylococcus aureus Skin Infection

2019 ◽  
pp. 139-147 ◽  
Author(s):  
Natalia Malachowa ◽  
Scott D. Kobayashi ◽  
Jamie Lovaglio ◽  
Frank R. DeLeo
Keyword(s):  
Staphylococcus Aureus ◽  
Mouse Model ◽  
Skin Infection

scholarly journals Relationship between Susceptibility to Daptomycin In Vitro and Activity In Vivo in a Rabbit Model of Aortic Valve Endocarditis

2009 ◽  
Vol 53 (4) ◽  
pp. 1463-1467 ◽  
Author(s):  
H. F. Chambers ◽  
L. Basuino ◽  
B. A. Diep ◽  
J. Steenbergen ◽  
S. Zhang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
Aortic Valve ◽  
Rabbit Model ◽  
Dual Infection ◽  
Survival Advantage ◽  
The Other ◽  
Infection Model

ABSTRACT Daptomycin is approved for treatment of Staphylococcus aureus bacteremia and right-sided endocarditis. Increases in daptomycin MICs have been associated with failure. A rabbit model of aortic valve endocarditis was used to determine whether MIC correlates with activity in vivo and whether a higher daptomycin dose can improve efficacy. Two related clinical S. aureus strains, one with a daptomycin MIC of 0.5 μg/ml and the other with a MIC of 2 μg/ml, were used to establish aortic valve endocarditis in rabbits. Daptomycin was administered once a day for 4 days at 12 mg/kg of body weight or 18 mg/kg to simulate doses in humans of 6 mg/kg and 10 mg/kg, respectively. Endocardial vegetations, spleens, and kidneys were harvested and quantitatively cultured. The strain with a MIC of 2 μg/ml had a survival advantage over the strain with a MIC of 0.5 μg/ml with >100 times more organisms of the former in endocardial vegetations at the 12-mg/kg dose in a dual-infection model. Both the 12-mg/kg dose and the 18-mg/kg dose completely eradicated the strain with a MIC of 0.5 from vegetations, spleens, and kidneys. The 12-mg/kg dose was ineffective against the strain with a MIC of 2 in vegetations; the 18-mg/kg dose produced a reduction of 3 log10 units in CFU in vegetations compared to the controls, although in no rabbit were organisms completely eliminated. Increasing the dose of daptomycin may improve its efficacy for infections caused by strains with reduced daptomycin susceptibility.

scholarly journals Exercise restores dysregulated gene expression in a mouse model of arrhythmogenic cardiomyopathy

2019 ◽  
Vol 116 (6) ◽  
pp. 1199-1213 ◽  
Author(s):  
Sirisha M Cheedipudi ◽  
Jinzhu Hu ◽  
Siyang Fan ◽  
Ping Yuan ◽  
Jennifer Karmouch ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Treadmill Exercise ◽  
Arrhythmogenic Cardiomyopathy ◽  
Transcript Levels ◽  
Myocardial Apoptosis ◽  
Genes Encoding ◽  
Canonical Wnt

Abstract Aims Arrhythmogenic cardiomyopathy (ACM) is a myocardial disease caused mainly by mutations in genes encoding desmosome proteins ACM patients present with ventricular arrhythmias, cardiac dysfunction, sudden cardiac death, and a subset with fibro-fatty infiltration of the right ventricle predominantly. Endurance exercise is thought to exacerbate cardiac dysfunction and arrhythmias in ACM. The objective was to determine the effects of treadmill exercise on cardiac phenotype, including myocyte gene expression in myocyte-specific desmoplakin (Dsp) haplo-insufficient (Myh6-Cre:DspW/F) mice. Methods and results Three months old sex-matched wild-type (WT) and Myh6-Cre:DspW/F mice with normal cardiac function, as assessed by echocardiography, were randomized to regular activity or 60 min of daily treadmill exercise (5.5 kJ work per run). Cardiac myocyte gene expression, cardiac function, arrhythmias, and myocardial histology, including apoptosis, were analysed prior to and after 3 months of routine activity or treadmill exercise. Fifty-seven and 781 genes were differentially expressed in 3- and 6-month-old Myh6-Cre:DspW/F cardiac myocytes, compared to the corresponding WT myocytes, respectively. Genes encoding secreted proteins (secretome), including inhibitors of the canonical WNT pathway, were among the most up-regulated genes. The differentially expressed genes (DEGs) predicted activation of epithelial–mesenchymal transition (EMT) and inflammation, and suppression of oxidative phosphorylation pathways in the Myh6-Cre:DspW/F myocytes. Treadmill exercise restored transcript levels of two-third (492/781) of the DEGs and the corresponding dysregulated transcriptional and biological pathways, including EMT, inflammation, and secreted inhibitors of the canonical WNT. The changes were associated with reduced myocardial apoptosis and eccentric cardiac hypertrophy without changes in cardiac function. Conclusion Treadmill exercise restored transcript levels of the majority of dysregulated genes in cardiac myocytes, reduced myocardial apoptosis, and induced eccentric cardiac hypertrophy without affecting cardiac dysfunction in a mouse model of ACM. The findings suggest that treadmill exercise has potential beneficial effects in a subset of cardiac phenotypes in ACM.

scholarly journals Therapeutic Efficacy of Halocidin-Derived Peptide HG1 in a Mouse Model of Surgical Wound Infection with Methicillin-ResistantStaphylococcus aureus

2011 ◽  
Vol 55 (3) ◽  
pp. 1296-1299 ◽  
Author(s):  
Young Shin Lee ◽  
Yong Pyo Shin ◽  
Seo Hwa Shin ◽  
Seungmi Park ◽  
Myung Hwa Kim ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Mouse Model ◽  
Skin Infection ◽  
Therapeutic Potential ◽  
Surgical Wound Infection ◽  
Infection Site ◽  
Surgical Wound ◽  
Topical Antibiotic ◽  
Wound Model ◽  
Bacterial Enumeration

ABSTRACTWe evaluated the therapeutic potential of HG1, an antimicrobial peptide, as a novel topical antibiotic by the use of a mouse surgical wound model of infection with methicillin-resistantStaphylococcus aureus. First, we attempted to determine whether or not HG1 infiltrated into the dermis when topically administered. Second, we evaluated the antibiotic effects of HG1 on skin infection via bacterial-enumeration and microscopic analyses. The results showed that topically administered HG1 was capable of penetrating into the dermis at the infection site, where it exerted its antimicrobial effects.

Sign in / Sign up

Export Citation Format

Share Document