scholarly journals Efficacy of Lantibiotic Treatment of Staphylococcus aureus-Induced Skin Infections, Monitored byIn VivoBioluminescent Imaging

2016 ◽  
Vol 60 (7) ◽  
pp. 3948-3955 ◽  
Author(s):  
Anton Du Preez van Staden ◽  
Tiaan Heunis ◽  
Carine Smith ◽  
Shelly Deane ◽  
Leon M. T. Dicks

ABSTRACTStaphylococcus aureusis a bacterial pathogen responsible for the majority of skin and soft tissue infections. Antibiotics are losing their efficacy as treatment for skin and soft tissue infections as a result of increased resistance in a variety of pathogens, includingS. aureus. It is thus imperative to explore alternative antimicrobial treatments to ensure future treatment options for skin and soft tissue infections. A select few lantibiotics, a group of natural defense peptides produced by bacteria, inhibit the growth of numerous clinicalS. aureusisolates, including methicillin-resistant strains. In this study, the antimicrobial activities of nisin, clausin, and amyloliquecidin, separately administered, were compared to that of a mupirocin-based ointment, which is commonly used as treatment forS. aureus-induced skin infections. Full-thickness excisional wounds, generated on the dorsal surfaces of mice, were infected with a bioluminescent strain ofS. aureus(strain Xen 36). The infections were monitored in real time usingin vivobioluminescent imaging. Lantibiotic treatments significantly reduced the bioluminescence ofS. aureusXen 36 to a level similar to that recorded with mupirocin treatment. Wound closure, however, was more pronounced during lantibiotic treatment. Lantibiotics thus have the potential to be used as an alternative treatment option forS. aureus-induced skin infections.

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Sanjay Chhibber ◽  
Ashu Shukla ◽  
Sandeep Kaur

ABSTRACT The emergence of drug resistance has rekindled interest in phage therapy as an alternative treatment option; its potency, safety, and proven efficacy are worth noting. However, phage therapy still suffers from issues of poor stability, narrow spectra, and poor pharmacokinetic profiles. Therefore, it is essential to look into the use of drug delivery systems for efficient delivery of lytic phages in vivo. The present study evaluated the use of nanostructured lipid-based carriers, i.e., transfersomes, as transdermal delivery systems for encapsulating a methicillin-resistant Staphylococcus aureus (MRSA) phage cocktail. Furthermore, the therapeutic potential of the encapsulated phage cocktail in resolving experimental soft tissue infections in rats was studied. Results from in vitro stability and in vivo phage titer experiments indicated that the transfersome-entrapped phage cocktail showed better persistence and stability than did free phages. Rats treated with the transfersome-entrapped phage cocktail resolved the experimental thigh infections within a period of 7 days, unlike the 20-day period required for untreated animals. The findings of the present study support the use of transfersomes as delivery agents to enhance the stability and in vivo persistence of the encapsulated phages. In addition, this study highlights the advantages offered by transfersome-encapsulated phages in providing better therapeutic options than free phages for treating skin and soft tissue infections. The transfersome-entrapped phage cocktail was able to protect all test animals (with no deaths) even when administered with a delay of 12 h postinfection, unlike free phages, thus making this treatment option more suitable for clinical settings.


2014 ◽  
Vol 21 (5) ◽  
pp. 622-627 ◽  
Author(s):  
Christopher P. Mocca ◽  
Rebecca A. Brady ◽  
Drusilla L. Burns

ABSTRACTDue to the emergence of highly virulent community-associated methicillin-resistantStaphylococcus aureus(CA-MRSA) infections,S. aureushas become a major threat to public health. A majority of CA-MRSA skin and soft tissue infections in the United States are caused byS. aureusUSA300 strains that are known to produce high levels of alpha hemolysin (Hla). Therefore, vaccines that contain inactivated forms of this toxin are currently being developed. In this study, we sought to determine the immune mechanisms of protection for this antigen using a vaccine composed of a genetically inactivated form of Hla (HlaH35L). Using a murine model of skin and soft tissue infections (SSTI), we found that BALB/c mice were protected by vaccination with HlaH35L; however, Jh mice, which are deficient in mature B lymphocytes and lack IgM and IgG in their serum, were not protected. Passive immunization with anti-HlaH35L antibodies conferred protection against bacterial colonization. Moreover, we found a positive correlation between the total antibody concentration induced by active vaccination and reduced bacterial levels. Animals that developed detectable neutralizing antibody titers after active vaccination were significantly protected from infection. These data demonstrate that antibodies to Hla represent the major mechanism of protection afforded by active vaccination with inactivated Hla in this murine model of SSTI, and in this disease model, antibody levels correlate with protection. These results provide important information for the future development and evaluation ofS. aureusvaccines.


2014 ◽  
Vol 53 (3) ◽  
pp. 810-815 ◽  
Author(s):  
Neha Kumar ◽  
Michael Z. David ◽  
Susan Boyle-Vavra ◽  
Julia Sieth ◽  
Robert S. Daum

Staphylococcus aureusis a commensal species that can also be a formidable pathogen. In the United States, an epidemic of community-acquired methicillin-resistantStaphylococcus aureus(MRSA) infections has been occurring for the last 15 years. In the context of a study in which we identified patients with skin and soft tissue infections (SSTIs) and randomized them to receive one of two antimicrobial treatment regimens, we assessedS. aureuscolonization in the nares, throat, and perianal skin on the day of enrollment and 40 days after therapy. We compared the prevalence of colonization between the SSTI patients and an uninfected control population. A total of 144 subjects and 130 controls, predominantly African American, participated in this study, and 116 returned for a 40-day follow-up visit. Of the SSTI patients, 76% were colonized withS. aureusat enrollment, as were 65% of the controls. Patients were more likely than the controls to be colonized with USA300 MRSA (62/144 [43.1%] versus 11/130 [8.5%], respectively;P< 0.001). The nares were not the most common site of colonization. The colonization prevalence diminished somewhat after antibiotic treatment but remained high. The isolates that colonized the controls were more likely than those in the patients to be methicillin-susceptibleS. aureus(MSSA) (74/84 [88.1%] versus 56/106 [52.8%], respectively;P< 0.001). In conclusion, the prevalence ofS. aureuscolonization among SSTI patients was high and often involved USA300 MRSA. The prevalence diminished somewhat with antimicrobial therapy but remained high at the 40-day follow-up visit. Control subjects were also colonized at a high prevalence but most often with a genetic background not associated with a clinical infection in this study.S. aureusis a commensal species and a pathogen. Plans for decolonization or eradication should take this distinction into account.


2021 ◽  
Vol 10 (43) ◽  
Author(s):  
Itidal Reslane ◽  
Margaret Sladek ◽  
Paul D. Fey ◽  
Baha Abdalhamid

Staphylococcus aureus is a major cause of skin and soft tissue infections as well as bloodstream infections worldwide. Here, we report the draft genome sequences of 18 deidentified S. aureus clinical strains collected from positive blood cultures.


2015 ◽  
Vol 53 (8) ◽  
pp. 2648-2658 ◽  
Author(s):  
Maria Pardos de la Gandara ◽  
Juan Antonio Raygoza Garay ◽  
Michael Mwangi ◽  
Jonathan N. Tobin ◽  
Amanda Tsang ◽  
...  

In November 2011, The Rockefeller University Center for Clinical and Translational Science (CCTS), the Laboratory of Microbiology and Infectious Diseases, and Clinical Directors Network (CDN) launched a research and learning collaborative project with six community health centers in the New York City metropolitan area to determine the nature (clonal type) of community-acquiredStaphylococcus aureusstrains causing skin and soft tissue infections (SSTIs). Between November 2011 and March 2013, wound and nasal samples from 129 patients with active SSTIs suspicious forS. aureuswere collected and characterized by molecular typing techniques. In 63 of 129 patients, the skin wounds were infected byS. aureus: methicillin-resistantS. aureus(MRSA) was recovered from 39 wounds and methicillin-sensitiveS. aureus(MSSA) was recovered from 24. Most—46 of the 63–wound isolates belonged to the CC8/Panton-Valentine leukocidin-positive (PVL+) group ofS. aureusclone USA300: 34 of these strains were MRSA and 12 were MSSA. Of the 63 patients withS. aureusinfections, 30 were also colonized byS. aureusin the nares: 16 of the colonizing isolates were MRSA, and 14 were MSSA, and the majority of the colonizing isolates belonged to the USA300 clonal group. In most cases (70%), the colonizing isolate belonged to the same clonal type as the strain involved with the infection. In three of the patients, the identity of invasive and colonizing MRSA isolates was further documented by whole-genome sequencing.


2014 ◽  
Vol 82 (9) ◽  
pp. 3588-3598 ◽  
Author(s):  
Stacey X. Xu ◽  
Kevin J. Gilmore ◽  
Peter A. Szabo ◽  
Joseph J. Zeppa ◽  
Miren L. Baroja ◽  
...  

ABSTRACTStaphylococcus aureusis a versatile bacterial pathogen that produces T cell-activating toxins known as superantigens (SAgs). Although excessive immune activation by SAgs can induce a dysregulated cytokine storm as a component of what is known as toxic shock syndrome (TSS), the contribution of SAgs to the staphylococcal infection process is not well defined. Here, we evaluated the role of the bacterial superantigen staphylococcal enterotoxin A (SEA) in a bacteremia model using humanized transgenic mice expressing SAg-responsive HLA-DR4 molecules. Infection withS. aureusNewman induced SEA-dependent Vβ skewing of T cells and enhanced bacterial survival in the liver compared with infection byseaknockout strain. SEA-induced gamma interferon, interleukin-12, and chemokine responses resulted in increased infiltration of CD11b+Ly6G+neutrophils into the liver, promoting the formation of abscesses that contained large numbers of viable staphylococci. Hepatic abscesses occurred significantly more frequently inS. aureusNewman-infected livers than in livers infected with the Newmanseaknockout strain, promoting the survival ofS. aureusin vivo. This represents a novel mechanism during infection wherebyS. aureusutilizes SAgs to form a specialized niche and manipulate the immune system.


mSphere ◽  
2021 ◽  
Author(s):  
Constance Duchesne ◽  
Nadira Frescaline ◽  
Océane Blaise ◽  
Jean-Jacques Lataillade ◽  
Sébastien Banzet ◽  
...  

Staphylococcus aureus is the most frequent cause of skin and soft tissue infections. Treatment failures are increasingly common due to antibiotic resistance and the emergence of resistant strains.


2011 ◽  
Vol 55 (5) ◽  
pp. 2431-2433 ◽  
Author(s):  
J. Chase McNeil ◽  
Kristina G. Hulten ◽  
Sheldon L. Kaplan ◽  
Edward O. Mason

ABSTRACTStaphylococcus aureusresistance to mupirocin is often caused by acquisition of a novel isoleucyl-tRNA synthetase encoded on the plasmid genemupA. We testedS. aureusisolates from children at Texas Children's Hospital with recurrent skin and soft tissue infections for mupirocin resistance andmupA. Of 136 isolates, 20 were resistant to mupirocin (14.7%). Fifteen isolates (11%) carriedmupA, and the gene was more common in methicillin-susceptibleS. aureus(21.4%) than methicillin-resistantS. aureus(8.3%;P= 0.03). Seven of 20 mupirocin-resistant isolates displayed clindamycin resistance.


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