Potential role of biofilms in deep cervical abscess

May, Jason G.; Shah, Priyanka A.; Sachdeva, Livjot; Micale, Mark A.; Kruper, Gregory J.; Sheyn, Anthony; Coticchia, James M.

doi:10.1016/j.ijporl.2013.09.009

Cited by 19 publications

(12 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The bacterial stringent response is a highly conserved (present in Gram-positive and Gram-negative bacteria) response to various stresses that impacts virulence and antibiotic susceptibility. Their unique ability to disrupt this stress response enables such peptides to show activity against stringent response controlled abscess infections, where biofilm phenotypes have also been suggested to play a crucial role [ 17 , 19 , 20 ]. In this context, although our peptides showed high MICs in vitro ( Table 1 ), we previously showed that they can reduce abscess sizes as well as have modest effects in reducing bacterial numbers when S .…”

Section: Resultsmentioning

confidence: 99%

Synergy between conventional antibiotics and anti-biofilm peptides in a murine, sub-cutaneous abscess model caused by recalcitrant ESKAPE pathogens

2018

View full text Add to dashboard Cite

With the antibiotic development pipeline running dry, many fear that we might soon run out of treatment options. High-density infections are particularly difficult to treat due to their adaptive multidrug-resistance and currently there are no therapies that adequately address this important issue. Here, a large-scale in vivo study was performed to enhance the activity of antibiotics to treat high-density infections caused by multidrug-resistant Gram-positive and Gram-negative bacteria. It was shown that synthetic peptides can be used in conjunction with the antibiotics ciprofloxacin, meropenem, erythromycin, gentamicin, and vancomycin to improve the treatment outcome of murine cutaneous abscesses caused by clinical hard-to-treat pathogens including all ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae) pathogens and Escherichia coli. Promisingly, combination treatment often showed synergistic effects that significantly reduced abscess sizes and/or improved clearance of bacterial isolates from the infection site, regardless of the antibiotic mode of action. In vitro data suggest that the mechanisms of peptide action in vivo include enhancement of antibiotic penetration and potential disruption of the stringent stress response.

show abstract

Section: Resultsmentioning

confidence: 99%

Synergy between conventional antibiotics and anti-biofilm peptides in a murine, sub-cutaneous abscess model caused by recalcitrant ESKAPE pathogens

2018

View full text Add to dashboard Cite

show abstract

“…It is tempting to speculate that the observed poor efficacy of antibiotics in our abscess model reflects either the high density of bacteria in the abscess or the fact that they were in a highly stressed state. Indeed, there has been some recent evidence suggesting that Gram-positive bacteria isolated from deep tissue abscesses are embedded in biofilm-like matrices (41). Consistent with this, pslD , a gene involved in exopolysaccharide biosynthesis, and mucC , a positive regulator gene for the synthesis of the exopolysaccharide alginate, were upregulated 5- to 7-fold.…”

Section: Discussionmentioning

confidence: 99%

New Mouse Model for Chronic Infections by Gram-Negative Bacteria Enabling the Study of Anti-Infective Efficacy and Host-Microbe Interactions

Pletzer

Mansour

Wuerth

et al. 2017

mBio

115

142

View full text Add to dashboard Cite

Only a few, relatively cumbersome animal models enable long-term Gram-negative bacterial infections that mimic human situations, where untreated infections can last for weeks. Here, we describe a simple murine cutaneous abscess model that enables chronic or progressive infections, depending on the subcutaneously injected bacterial strain. In this model, Pseudomonas aeruginosa cystic fibrosis epidemic isolate LESB58 caused localized high-density skin and soft tissue infections and necrotic skin lesions for up to 10 days but did not disseminate in either CD-1 or C57BL/6 mice. The model was adapted for use with four major Gram-negative nosocomial pathogens, Acinetobacter baumannii, Klebsiella pneumoniae, Enterobacter cloacae, and Escherichia coli. This model enabled noninvasive imaging and tracking of lux-tagged bacteria, the influx of activated neutrophils, and production of reactive oxygen-nitrogen species at the infection site. Screening antimicrobials against high-density infections showed that local but not intravenous administration of gentamicin, ciprofloxacin, and meropenem significantly but incompletely reduced bacterial counts and superficial tissue dermonecrosis. Bacterial RNA isolated from the abscess tissue revealed that Pseudomonas genes involved in iron uptake, toxin production, surface lipopolysaccharide regulation, adherence, and lipase production were highly upregulated whereas phenazine production and expression of global activator gacA were downregulated. The model was validated for studying virulence using mutants of more-virulent P. aeruginosa strain PA14. Thus, mutants defective in flagella or motility, type III secretion, or siderophore biosynthesis were noninvasive and suppressed dermal necrosis in mice, while a strain with a mutation in the bfiS gene encoding a sensor kinase showed enhanced invasiveness and mortality in mice compared to controls infected with wild-type P. aeruginosa PA14.

show abstract

“…This correlates with recent studies that demonstrated the importance of Usp2 in responding to amino acid starvation (Attia et al, 2013). Biofilm formation is a survival strategy for bacteria to adapt to hostile environments and although bacteria in abscesses are largely considered to be loosely associated in pus, recent evidence suggests that bacteria isolated from deep tissue abscesses are embedded in biofilm-like matrices (May et al, 2014). Of great importance, recurring abscesses and biofilms are similarly recalcitrant to antibiotic therapy (Davies, 2003, Stearne et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Bacterial Abscess Formation Is Controlled by the Stringent Stress Response and Can Be Targeted Therapeutically

et al. 2016

View full text Add to dashboard Cite

Cutaneous abscess infections are difficult to treat with current therapies and alternatives to conventional antibiotics are needed. Understanding the regulatory mechanisms that govern abscess pathology should reveal therapeutic interventions for these recalcitrant infections. Here we demonstrated that the stringent stress response employed by bacteria to cope and adapt to environmental stressors was essential for the formation of lesions, but not bacterial growth, in a methicillin resistant Staphylococcus aureus (MRSA) cutaneous abscess mouse model. To pharmacologically confirm the role of the stringent response in abscess formation, a cationic peptide that causes rapid degradation of the stringent response mediator, guanosine tetraphosphate (ppGpp), was employed. The therapeutic application of this peptide strongly inhibited lesion formation in mice infected with Gram-positive MRSA and Gram-negative Pseudomonas aeruginosa. Overall, we provide insights into the mechanisms governing abscess formation and a paradigm for treating multidrug resistant cutaneous abscesses.

show abstract

Potential role of biofilms in deep cervical abscess

Cited by 19 publications

References 21 publications

Synergy between conventional antibiotics and anti-biofilm peptides in a murine, sub-cutaneous abscess model caused by recalcitrant ESKAPE pathogens

Synergy between conventional antibiotics and anti-biofilm peptides in a murine, sub-cutaneous abscess model caused by recalcitrant ESKAPE pathogens

New Mouse Model for Chronic Infections by Gram-Negative Bacteria Enabling the Study of Anti-Infective Efficacy and Host-Microbe Interactions

Bacterial Abscess Formation Is Controlled by the Stringent Stress Response and Can Be Targeted Therapeutically

Contact Info

Product

Resources

About