IMPORTANCE OF LIPOOLIGOSACCHARIDE STRUCTURE IN DETERMINING GONOCOCCAL RESISTANCE TO HYDROPHOBIC ANTIMICROBIAL AGENTS RESULTING FROM THE MTR EFFLUX SYSTEM

被引:40
作者
LUCAS, CE
HAGMAN, KE
LEVIN, JC
STEIN, DC
SHAFER, WM
机构
[1] EMORY UNIV, SCH MED, DEPT MICROBIOL & IMMUNOL, ATLANTA, GA 30322 USA
[2] VET ADM MED CTR, VA MED RES SERV, MICROBIAL PATHOGENESIS LAB, ATLANTA, GA 30033 USA
[3] UNIV MARYLAND, DEPT MICROBIOL & IMMUNOL, COLLEGE PK, MD 20742 USA
关键词
D O I
10.1111/j.1365-2958.1995.tb02325.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Levels of gonococcal resistance to antimicrobial hydrophobic agents (HAs) are controlled by the mtr (multiple transferrable resistance) system, composed of the mtrRCDE genes. The mtrR gene encodes a transcriptional repressor that appears to regulate expression of the upstream and divergent mtrCDE operon. The mtrCDE genes encode membrane proteins analogous to the MexABOprK proteins of Pseudomonas aeruginosa that mediate export of structurally diverse antimicrobial agents. In this study we found that a single base pair deletion in a 13 bp inverted repeat sequence within the mtrR promoter resulted in increased resistance of gonococci to both crystal violet (CV) and erythromycin (ERY) as well as to the more lipophilic non-ionic detergent Triton X-100 (TX-100). However, this cross-resistance was contingent on the production of a full-length lipooligosaccharide (LOS) by the recipient strain used in transformation experiments. Introduction of this mutation (mtrR-171) into three chemically distinct deep-rough LOS mutants by transformation resulted in a fourfold increase in resistance to TX-100 compared with a 160-fold increase in an isogenic strain producing a full-length LOS. However, both wild-type and deep-rough LOS strains exhibited an eightfold increase in resistance to CV and ERY as a result of the mtrR-171 mutation. This suggests that gonococci have different LOS structural requirements for mtr-mediated resistance to HAs that differ in their lipophilic properties. Evidence is presented that gonococci exclude HAs by an energy dependent efflux process mediated by the mtr system.
引用
收藏
页码:1001 / 1009
页数:9
相关论文
共 38 条
[1]   PURIFICATION AND PARTIAL CHARACTERIZATION OF THE MAJOR OUTER-MEMBRANE PROTEIN OF NEISSERIA-GONORRHOEAE [J].
BLAKE, MS ;
GOTSCHLICH, EC .
INFECTION AND IMMUNITY, 1982, 36 (01) :277-283
[2]   CONSTRUCTION OF ISOGENIC GONOCOCCI WITH VARIABLE PORIN STRUCTURE - EFFECTS ON SUSCEPTIBILITY TO HUMAN SERUM AND ANTIBIOTICS [J].
CARBONETTI, N ;
SIMNAD, V ;
ELKINS, C ;
SPARLING, PF .
MOLECULAR MICROBIOLOGY, 1990, 4 (06) :1009-1018
[3]   MOLECULAR-CLONING AND CHARACTERIZATION OF THE STRUCTURAL GENE FOR PROTEIN-I, THE MAJOR OUTER-MEMBRANE PROTEIN OF NEISSERIA-GONORRHOEAE [J].
CARBONETTI, NH ;
SPARLING, PF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (24) :9084-9088
[4]   INVESTIGATION OF THE STRUCTURAL HETEROGENEITY OF LIPOOLIGOSACCHARIDES FROM PATHOGENIC HAEMOPHILUS AND NEISSERIA SPECIES AND OF R-TYPE LIPOPOLYSACCHARIDES FROM SALMONELLA-TYPHIMURIUM BY ELECTROSPRAY MASS-SPECTROMETRY [J].
GIBSON, BW ;
MELAUGH, W ;
PHILLIPS, NJ ;
APICELLA, MA ;
CAMPAGNARI, AA ;
GRIFFISS, JM .
JOURNAL OF BACTERIOLOGY, 1993, 175 (09) :2702-2712
[5]   THE IMMUNOCHEMISTRY OF NEISSERIAL LOS [J].
GRIFFISS, JM ;
SCHNEIDER, H ;
MANDRELL, RE ;
JARVIS, GA ;
KIM, JJ ;
GIBSON, B ;
APICELLA, MA .
ANTONIE VAN LEEUWENHOEK JOURNAL OF MICROBIOLOGY, 1987, 53 (06) :501-507
[6]   ALTERED CRYSTAL VIOLET PERMEABILITY AND LYTIC BEHAVIOR IN ANTIBIOTIC-RESISTANT AND ANTIBIOTIC-SENSITIVE MUTANTS OF NEISSERIA-GONORRHOEAE [J].
GUYMON, LF ;
SPARLING, PF .
JOURNAL OF BACTERIOLOGY, 1975, 124 (02) :757-763
[7]   PYOCIN-RESISTANT LIPOPOLYSACCHARIDE MUTANTS OF NEISSERIA-GONORRHOEAE - ALTERATIONS IN SENSITIVITY TO NORMAL HUMAN-SERUM AND POLYMYXIN-B [J].
GUYMON, LF ;
ESSER, M ;
SHAFER, WM .
INFECTION AND IMMUNITY, 1982, 36 (02) :541-547
[8]   RESISTANCE OF NEISSERIA-GONORRHOEAE TO ANTIMICROBIAL HYDROPHOBIC AGENTS IS MODULATED BY THE MTRRCDE EFFLUX SYSTEM [J].
HAGMAN, KE ;
PAN, WB ;
SPRATT, BG ;
BALTHAZAR, JT ;
JUDD, RC ;
SHAFER, WM .
MICROBIOLOGY-SGM, 1995, 141 :611-622
[9]  
HAGMAN KE, 1995, IN PRESS J BACTERIOL
[10]   MORPHOLOGICAL HETEROGENEITY AMONG SALMONELLA LIPOPOLYSACCHARIDE CHEMOTYPES IN SILVER-STAINED POLYACRYLAMIDE GELS [J].
HITCHCOCK, PJ ;
BROWN, TM .
JOURNAL OF BACTERIOLOGY, 1983, 154 (01) :269-277