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8. Hydrogen Peroxide, Povidone-Iodine and Chlorhexidine Fail to Eradicate Staphylococcus aureus Biofilm from Infected Implant Materials

Author

Parker, Dana M., Koch, John A., Gish, Charles G., Brothers, Kimberly M., Li, William, Gilbertie, Jessica, Rowe, Sarah E., Conlon, Brian P., Byrapogu, Venkata K. C., Urish, Kenneth L., Parker, Dana M., Koch, John A., Gish, Charles G., Brothers, Kimberly M., Li, William, Gilbertie, Jessica, Rowe, Sarah E., Conlon, Brian P., Byrapogu, Venkata K. C., and Urish, Kenneth L.

Abstract

Hydrogen peroxide, povidone-iodine, and chlorhexidine are antiseptics that are commonly added to irrigants to either prevent or treat infection. There are little clinical data available that demonstrate efficacy of adding antiseptics to irrigants in the treatment of periprosthetic joint infection after biofilm establishment. The objective of the study was to assess the bactericidal activity of the antiseptics on S. aureus planktonic and biofilm. For planktonic irrigation, S. aureus was exposed to different concentrations of antiseptics. S. aureus biofilm was developed by submerging a Kirschner wire into normalized bacteria and allowing it to grow for forty-eight hours. The Kirschner wire was then treated with irrigation solutions and plated for CFU analysis. Hydrogen peroxide, povidone-iodine, and chlorhexidine were bactericidal against planktonic bacteria with over a 3 log reduction (p < 0.0001). Unlike cefazolin, the antiseptics were not bactericidal (less than 3 log reduction) against biofilm bacteria but did have a statistical reduction in biofilm as compared to the initial time point (p < 0.0001). As compared to cefazolin treatment alone, the addition of hydrogen peroxide or povidone-iodine to cefazolin treatment only additionally reduced the biofilm burden by less than 1 log. The antiseptics demonstrated bactericidal properties with planktonic S. aureus; however, when used to irrigate S. aureus biofilms, these antiseptics were unable to decrease biofilm mass below a 3 log reduction, suggesting that S. aureus biofilm has a tolerance to antiseptics. This information should be considered when considering antibiotic tolerance in established S. aureus biofilm treatment.

Published
2023

10. Engineered peptide PLG0206 overcomes limitations of a challenging antimicrobial drug class

Author

Huang, David B., primary, Brothers, Kimberly M., additional, Mandell, Jonathan B., additional, Taguchi, Masashi, additional, Alexander, Peter G., additional, Parker, Dana M., additional, Shinabarger, Dean, additional, Pillar, Chris, additional, Morrissey, Ian, additional, Hawser, Stephen, additional, Ghahramani, Parviz, additional, Dobbins, Despina, additional, Pachuda, Nicholas, additional, Montelaro, Ronald, additional, Steckbeck, Jonathan D., additional, and Urish, Kenneth L., additional

Published
2022
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17. Prospective Activity of PLG0206, an Engineered Antimicrobial Peptide, on Chronic Periprosthetic Joint Infection Total Knee Arthroplasty Components Ex Vivo : The Knee Explant Analysis (KnEA) Study

Author

Huang, David, primary, Parker, Dana, additional, Mandell, Jonathan B., additional, Brothers, Kimberly M., additional, Gish, Charles G., additional, Koch, John A., additional, Pachuda, Nicholas, additional, Dobbins, Despina, additional, Steckbeck, Jonathan, additional, and Urish, Kenneth L., additional

Published
2021
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18. The Staphylococcus aureus toxin–antitoxin system YefM–YoeB is associated with antibiotic tolerance and extracellular dependent biofilm formation

Author

Qi, Xinyu, Brothers, Kimberly M., Ma, Dongzhu, Mandell, Jonathan B., Donegan, Niles P., Cheung, Ambrose L., Richardson, Anthony R., and Urish, Kenneth L.

Subjects
biochemical phenomena, metabolism, and nutrition
Abstract

The high antibiotic tolerance of Staphylococcus aureus biofilms is associated with challenges for treating periprosthetic joint infection. The toxin–antitoxin system, YefM–YoeB, is thought to be a regulator for antibiotic tolerance, but its physiological role is unknown. The objective of this study was to determine the biofilm and antibiotic susceptibility phenotypes associated with S. aureus yoeB homologs. We hypothesized the toxin–antitoxin yoeB homologs contribute to biofilm formation and antibiotic susceptibility. Disruption of yoeB1 and yoeB2 resulted in decreased biofilm formation in comparison to Newman and JE2 wild-type (WT) S. aureus strains. In comparison to yoeB mutants, both Newman and JE2 WT strains had higher polysaccharide intercellular adhesin (PIA) production. Treatment with sodium metaperiodate increased biofilm formation in Newman WT, indicating biofilm formation may be increased under conditions of oxidative stress. DNase I treatment decreased biofilm formation in Newman WT but not in the absence of yoeB1 or yoeB2. Additionally, WT strains had a higher extracellular DNA (eDNA) content in comparison to yoeB mutants but no differences in biofilm protein content. Moreover, loss of yoeB1 and yoeB2 decreased biofilm survival in both Newman and JE2 strains. Finally, in a neutropenic mouse abscess model, deletion of yoeB1 and yoeB2 resulted in reduced bacterial burden. In conclusion, our data suggest that yoeB1 and yoeB2 are associated with S. aureus planktonic growth, extracellular dependent biofilm formation, antibiotic tolerance, and virulence.

Published
2021

23. BifA, a cyclic-Di-GMP phosphodiesterase, inversely regulates biofilm formation and swarming motility by Pseudomonas aeruginosa PA14

Author

Kuchma, Sherry L., Brothers, Kimberly M., Merritt, Judith H., Liberati, Nicole T., Ausubel, Frederick M., and O'Toole, George A.

Subjects
Pseudomonas aeruginosa -- Physiological aspects, Phosphodiesterases -- Physiological aspects, Microbial mats -- Growth, Bacteria -- Motility, Bacteria -- Physiological aspects, Company growth, Biological sciences
Abstract

The intracellular signaling molecule, cyclie-di-GMP (e-di-GMP), has been shown to influence bacterial behaviors, including motility and biofilm formation. We report the identification and characterization of PA4367, a gene involved in regulating surface-associated behaviors in Pseudomonas aeruginosa. The PA4367 gene encodes a protein with an EAL domain, associated with e-di-GMP phosphodiesterase activity, as well as a GGDEF domain, which is associated with a c-di-GMP-synthesizing diguanylate cyclase activity. Deletion of the PA4367 gene results in a severe defect in swarming motility and a hyperbiofilm pbenotype; thus, we designate this gene bifA, for biofilm formation. We show that BifA localizes to the inner membrane and, in biochemical studies, that purified BifA protein exhibits phosphodiesterase activity in vitro but no detectable diguanylate eyclase activity. Furthermore, mutational analyses of the conserved EAL and GGDEF residues of BifA suggest that both domains are important for the observed phosphodiesterase activity. Consistent with these data, the [DELTA]bifA mutant exhibits increased cellular pools of c-di-GMP relative to the wild type and increased synthesis of a polysaccharide produced by the pel locus. This increased polysaccharide production is required for the enhanced biofilm formed by the [DELTA]bifA mutant but does not contribute to the observed swarming defect. The [DELTA]bifA mutation also results in decreased flagellar reversals. Based on epistasis studies with the previously described sadB gene, we propose that BifA functions upstream of SadB in the control of biofilm formation and swarming.

Published
2007

24. SadC reciprocally influences biofilm formation and swarming motility via modulation of exopolysaccharide production and flagellar function

Author

Merritt, Judith H., Brothers, Kimberly M., Kuchma, Sherry L., and O'Toole, George A.

Subjects
Microbial mats -- Growth, Microbial mats -- Genetic aspects, Pseudomonas aeruginosa -- Genetic aspects, Company growth, Biological sciences
Abstract

Pseudomonas aeruginosa has served as an important organism in the study of biofilm formation; however, we still lack an understanding of the mechanisms by which this microbe transitions to a surface lifestyle. A recent study of the early stages of biofilm formation implicated the control of flagellar reversals and production of an exopolysaccharide (EPS) as factors in the establishment of a stable association with the substratum and swarming motility. Here we present evidence that SadC (PA4332), an inner membrane-localized diguanylate cyclase, plays a role in controlling these cellular functions. Deletion of the sadC gene results in a strain that is defective in biofilm formation and a hyperswarmer, while multicopy expression of this gene promotes sessility. A [DELTA]sadC mutant was additionally found to be deficient in EPS production and display altered reversal behavior while swimming in high-viscosity medium, two behaviors proposed to influence biofilm formation and swarming motility. Epistasis analysis suggests that the sadC gene is part of a genetic pathway that allows for the concomitant regulation of these aspects of P. aeruginosa surface behavior. We propose that SadC and the phosphodiesterase BifA (S. L. Kuchma et al., J. Bacteriol. 189:8165-8178, 2007), via modulating levels of the signaling molecule cyclic-di-GMP, coregulate swarming motility and biofilm formation as P. aeruginosa transitions from a planktonic to a surface-associated lifestyle.

Published
2007

25. Inverse regulation of biofilm formation and swarming motility by Pseudomonas aeruginosa PA14

Author

Caiazza, Nicky C., Merritt, Judith H., Brothers, Kimberly M., and O'Toole, George A.

Subjects
Pseudomonas aeruginosa -- Genetic aspects, Pseudomonas aeruginosa -- Research, Genetic regulation -- Research, Microbial mats -- Research, Gene mutations -- Research, Biological sciences
Abstract

We previously reported that SadB, a protein of unknown function, is required for an early step in biofilm formation by the opportunistic pathogen Pseudomonas aeruginosa. Here we report that a mutation in sadB also results in increased swarming compared to the wild-type strain. Our data are consistent with a model in which SadB inversely regulates biofilm formation and swarming motility via its ability both to modulate flagellar reversals in a viscosity-dependent fashion and to influence the production of the Pel exopolysaccharide. We also show that SadB is required to properly modulate flagellar reversal rates via chemotaxis cluster IV (CheIV cluster). Mutational analyses of two components of the CheIV cluster, the methyl-accepting chemotaxis protein PilJ and the PilJ demethylase ChpB, support a model wherein this chemotaxis cluster participates in the inverse regulation of biofilm formation and swarming motility. Epistasis analysis indicates that SadB functions upstream of the CheIV cluster. We propose that P. aeruginosa utilizes a SadB-dependent, chemotaxis-like regulatory pathway to inversely regulate two key surface behaviors, biofilm formation and swarming motility. doi:10.1128/JB.01685-06

Published
2007

32. Staphylococcus aureus genotype variation among and within periprosthetic joint infections.

Author

Ma, Dongzhu, Brothers, Kimberly M., Maher, Patrick L., Phillips, Nathan J., Simonetti, Deborah, William Pasculle, Anthony, Richardson, Anthony R., Cooper, Vaughn S., and Urish, Kenneth L.

Subjects
*JOINT infections, *STAPHYLOCOCCUS aureus, *MICROCOCCACEAE, *WHOLE genome sequencing, *GENETIC variation, *GENOTYPES, *FIBRONECTINS
Abstract

Staphylococcus aureus is a common organism in orthopedic infections, but little is known about the genetic diversity of strains during an infectious process. Using periprosthetic joint infection (PJI) as a model, a prospective study was designed to quantify genetic variation among S. aureus strains both among and within patients. Whole genome sequencing and multilocus sequence typing was performed to genotype these two populations at high resolution. In nasal cultures, 78% of strains were of clonal complexes CC5, CC8, and CC30. In PJI cultures, only 63% could be classified in these common clonal complexes. The PJI cultures had a larger proportion of atypical strains, and these atypical strains were associated with poor host status and compromised immune conditions. Mutations in genes involved in fibronectin binding (ebh, fnbA, clfA, and clfB) systematically distinguished later PJI isolates from the first PJI isolate from each patient. Repeated mutations in S. aureus genes associated with extracellular matrix binding were identified, suggesting adaptive, parallel evolution of S. aureus during the development of PJI. [ABSTRACT FROM AUTHOR]

Published
2022
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33. Blowing epithelial cell bubbles with GumB: ShlA-family pore-forming toxins induce blebbing and rapid cellular death in corneal epithelial cells

Author

Brothers, Kimberly M., primary, Callaghan, Jake D., additional, Stella, Nicholas A., additional, Bachinsky, Julianna M., additional, AlHigaylan, Mohammed, additional, Lehner, Kara L., additional, Franks, Jonathan M., additional, Lathrop, Kira L., additional, Collins, Elliot, additional, Schmitt, Deanna M., additional, Horzempa, Joseph, additional, and Shanks, Robert M. Q., additional

Published
2019
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36. Gene Acquisition by a Distinct Phyletic Group within Streptococcus pneumoniae Promotes Adhesion to the Ocular Epithelium

Author

Antic, Irena, primary, Brothers, Kimberly M., additional, Stolzer, Maureen, additional, Lai, Han, additional, Powell, Evan, additional, Eutsey, Rory, additional, Cuevas, Rolando A., additional, Miao, Xinyu, additional, Kowalski, Regis P., additional, Shanks, Robert M. Q., additional, Durand, Dannie, additional, and Hiller, N. Luisa, additional

Published
2017
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38. Predatory bacteria are nontoxic to the rabbit ocular surface

Author

Romanowski, Eric G., primary, Stella, Nicholas A., additional, Brothers, Kimberly M., additional, Yates, Kathleen A., additional, Funderburgh, Martha L., additional, Funderburgh, James L., additional, Gupta, Shilpi, additional, Dharani, Sonal, additional, Kadouri, Daniel E., additional, and Shanks, Robert M. Q., additional

Published
2016
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