University of Iowa microbiologist Alexander Horswill discussed new ways of treating antibiotic resistant Staphylococcus aureus (Staph) at Monday’s immunology and microbiology lecture at the Dartmouth-Hitchcock Medical Center.
Staphylococcus is a coccal Gram-positive bacteria that can cause a wide range of illnesses from simple carbuncles to life-threatening diseases such as meningitis and endocarditis. Coccal refers to staph’s round shape and Gram-positive means that staph’s high peptidoglycan content in the cell wall is able to retain dye from Gram-staining, which results in a dark blue or purple color, rather than a lighter pink or red of Gram-negative bacteria.
Twenty percent of the American population is persistently colonized with Staph, which is spread primarily via human-to-human contact. Horswill’s lecture centered on not only the dangers of Staphilococcus’ prevalence, but also its propensity for becoming resistant to antibiotics.
Ninety-eight percent of staph strains are currently resistant to penicillin and 50-70 percent of strains are resistant to methicillin. This leaves only vancomycin, against which at least three Staphilococcus strains have developed resistance.
Staphilococcus is difficult to treat because it can bind to organic substances such as skin, as well as inorganic surfaces, such as prosthetic limbs or hearts. After coming in contact with a moist surface, Staphilococcus autolyses in order to create a matrix of DNA and cells, which is known as a biofilm.
Biofilms, which are the main cause of chronic infections, are both anti-inflammatory and resistant to anti-microbials. These characteristics make them extremely difficult to remove.
Horswill’s research focuses on using the Staphilococcus’s quorum sensing system against it in order to reverse the process of biofilm construction.
Quorum sensing is a method in which bacteria regulate growth by coordinating gene expression according to population density. By accessing this communication pathway, Horswill has been able to induce dispersion of biofilms.
In Staphilococcus, quorum sensing is activated by auto-inducing peptides (AIP), which are produced by the Staphilococcus bacteria. These peptides trigger the release of proteases, which break up the tough biofilms and return the Staphilococcus to a planktonic state, which makes it substantially more susceptible to antibiotics.
By using intein-catalyzed protein splicing, which manipulates catalytic reactions to create customized proteins, Horwill’s team was able to produce AIP in large levels in order to unravel many of Staphilococcus’ peptide-regulated relationships. The goal of this research is a therapeutic application, which could potentially treat antibiotic resistant Staphilococcus.
Horswill’s main tactic in decoding the quorum sensing actions of bacteria was to search for Staphilococcus mutants that were unable to form biofilms. He discovered that AIP not only turns on proteases, but deoxyribonucleases (DNase) as well. Nucleases such as DNase, as it turns out, make the biofilms fall apart.
By beginning to unlock Staphilococcus’ own regulatory methods Horswill has taken a step closer toward medical application.
“These agents are coming back and have not cooperated with our antibiotic pressure,” Horswill said.