TY - JOUR
T1 - In vitro characterization of multivalent adhesion molecule 7-based inhibition of multidrug-resistant bacteria isolated from wounded military personnel
AU - Krachler, Anne Marie
AU - Mende, Katrin
AU - Murray, Clinton
AU - Orth, Kim
N1 - Funding Information:
We would like to thank the Orth lab for critical reading and comments on the manuscript. K.O. and A.M.K. are supported by grants from NIH-Allergy and Infectious Disease (R01-AI056404 and R01-AI087808) and the Welch Foundation (I-1561). K.O. is a Burroughs Wellcome Investigator in Pathogenesis of Infectious Disease and a W.W. Caruth Jr. Biomedical Scholar. This work was also supported by the Armed Forces Health Surveillance Center including the Global Emerging Infectious System. The views expressed herein are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense or the US Government. K.M. and C.M. are employees of the US government. This work was prepared as part of their official duties and, as such, there is no copyright to be transferred.
PY - 2012
Y1 - 2012
N2 - 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 b-lactamaseproducing 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.
AB - 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 b-lactamaseproducing 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.
KW - Acinetobacter
KW - Adhesin
KW - Anti-adhesion treatment
KW - Bacterial attachment
KW - Klebsiella
KW - MAM7
KW - Multidrug-resistance
KW - Pseudomonas
KW - Wound infections
UR - http://www.scopus.com/inward/record.url?scp=84866492320&partnerID=8YFLogxK
U2 - 10.4161/viru.20816
DO - 10.4161/viru.20816
M3 - Article
C2 - 22722243
AN - SCOPUS:84866492320
SN - 2150-5594
VL - 3
SP - 389
EP - 399
JO - Virulence
JF - Virulence
IS - 4
ER -