In vitro characterization of multivalent adhesion molecule 7-based inhibition of multidrug-resistant bacteria isolated from wounded military personnel.
Treatment of wounded military personnel at military medical centers is often complicated by colonization and infection of wounds with pathogenic bacteria. These include nosocomially transmitted, often multidrug-resistant pathogens such as Acinetobacter baumannii-calcoaceticus complex, Pseudomonas aeruginosa and extended spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae. We analyzed the efficacy of multivalent adhesion molecule (MAM) 7-based anti-adhesion treatment of host cells against aforementioned pathogens in a tissue culture infection model. Herein, we observed that a correlation between two important hallmarks of virulence, attachment and cytotoxicity, could serve as a useful predictor for the success of MAM7-based inhibition against bacterial infections. Initially, we characterized 20 patient isolates (five from each pathogen mentioned above) in terms of genotypic diversity, antimicrobial susceptibility and important hallmarks of pathogenicity (biofilm formation, attachment to and cytotoxicity toward cultured host cells). All isolates displayed a high degree of genotypic diversity, which was also reflected by large strain-to-strain variability in terms of biofilm formation, attachment and cytotoxicity within each group of pathogen. Using non-pathogenic bacteria expressing MAM7 or latex beads coated with recombinant MAM7 for anti-adhesion treatment, we showed a decrease in cytotoxicity, indicating that MAM7 has potential as a prophylactic agent to attenuate infection by multidrug-resistant bacterial pathogens.
Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA.
Anne Marie
AM
Krachler
Katrin
K
Mende
Clinton
C
Murray
Kim
K
Orth
D018829:Adhesins, Bacterial / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001422:Bacterial Adhesion / Q000187:drug effects; D002470:Cell Survival; D003428:Cross Infection / Q000188:drug therapy / Q000382:microbiology; D024901:Drug Resistance, Multiple, Bacterial; D014644:Genetic Variation; D006090:Gram-Negative Bacteria / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification / Q000472:pathogenicity; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008889:Military Personnel; D014946:Wound Infection / Q000188:drug therapy / Q000382:microbiology*
D018829:Adhesins, Bacterial; D000900:Anti-Bacterial Agents