(567f) Antibody-Therapeutic Targeting of Antibiotic-Resistant Outer Membrane Proteins in Escherichia Coli

Li, H., Sun Yat-sen University
Lin, X., Sun Yat-sen University
Zhang, B., Sun Yat-sen University
Yang, M., Sun Yat-sen University
Peng, X., Sun Yat-sen University

Recently, the increasing incidence of antibiotic-resistant bacteria has been come forth due to inappropriate and too frequent use of antibiotics. The antibiotic-resistant bacteria that were once susceptible to antibiotics are becoming more and more difficult to be treated by antibiotics, and thus pose a serious threat to human health today. Thus, it is urgent to develop novel strategies to control the bacteria. In the current study, comparative proteomic methodologies were used for identification of sharedly altered outer membrane proteins (OM proteins) that are responsible for chloramphenical (CAP)-resistant E. coli and for survival in medium with suddenly strong CAP treatment. Six differential OM proteins and an unknown location protein were determined to be sharedly CAP-resistant-related proteins with the use of 2-DE/MS, Western blotting and gene mutant methods, in which TolC, OmpT, OmpC and OmpW were critical altered proteins and potential targets for the designation of the new drugs. Furthermore, a novel method of specific antibody combating bacterial growth was developed on these OM proteins. Only anti-TolC showed a very significant inhibition on bacterial growth in medium with CAP when antisera to TolC, OmpC, OmpT and OmpW were separately applied. The growth of CAP-resistant E. coli and its original strain was completely inhibited when they bound with anti-TolC and survived in 1/8 MIC of CAP, which was equal to behavior of ¢tolC when it did in the same concentration of the antibiotic. Furthermore, the experiment was performed in vivo, showing significant inhibition on clinic antibiotic-resistant E. coli strain. Our study suggests that combination therapy involving antibiotics that enhance the expression of an antibody target could be far more effective than either drug alone, which gives a novel insight into therapy to infection by antibiotic-resistant bacteria.