Zhang L, Li X Z, Poole K
Department of Microbiology and Immunology, Queen's University, Kingston, Ontario K7L 3N6, Canada.
Antimicrob Agents Chemother. 2000 Feb;44(2):287-93. doi: 10.1128/AAC.44.2.287-293.2000.
Clinical strains of Stenotrophomonas maltophilia are often highly resistant to multiple antibiotics, although the mechanisms of resistance are generally poorly understood. Multidrug resistant (MDR) strains were readily selected by plating a sensitive reference strain of the organism individually onto a variety of antibiotics, including tetracycline, chloramphenicol, ciprofloxacin, and norfloxacin. Tetracycline-selected MDR strains typically showed cross-resistance to erythromycin and fluoroquinolones and, in some instances, aminoglycosides. MDR mutants selected with the other agents generally displayed resistance to chloramphenicol and fluoroquinolones only, although two MDR strains (e.g., K1385) were also resistant to erythromycin and hypersusceptible to aminoglycosides. Many of the MDR strains expressed either moderate or high levels of a novel outer membrane protein (OMP) of ca. 50 kDa molecular mass, a phenotype typical of MDR strains of Pseudomonas aeruginosa hyperexpressing drug efflux systems. Indeed, the 50-kDa OMP of these S. maltophilia MDR strains reacted with antibody to OprM, the outer membrane component of the MexAB-OprM MDR efflux system of P. aeruginosa. Similarly, a ca. 110-kDa cytoplasmic membrane protein of these MDR strains also reacted with antibody to the MexB component of the P. aeruginosa pump. The outer and cytoplasmic membranes of several clinical S. maltophilia strains also reacted with the anti-OprM and anti-MexB antibodies. N-terminal amino acid sequencing of a cyanogen bromide-generated peptide of the 50-kDa OMP of MDR strain K1385, dubbed SmeM (Stenotrophomonas multidrug efflux), revealed it to be very similar to a number of outer membrane multidrug efflux components of P. aeruginosa and Pseudomonas putida. Deletion of the L1 and L2 beta-lactamase genes confirmed that these enzymes were responsible for the bulk of the beta-lactam resistance of K1385 and its parent. Still, overexpression of the MDR efflux mechanism in an L1- and L2-deficient derivative of K1385 did yield a modest increase in resistance to a few beta-lactams. These data are consistent with the MDR efflux mechanism(s) playing a role in the multidrug resistance of S. maltophilia.
嗜麦芽窄食单胞菌的临床菌株通常对多种抗生素具有高度耐药性，尽管耐药机制一般还不太清楚。通过将该生物体的敏感参考菌株分别接种到多种抗生素上，包括四环素、氯霉素、环丙沙星和诺氟沙星，很容易筛选出多药耐药（MDR）菌株。四环素筛选出的MDR菌株通常对红霉素和氟喹诺酮类药物表现出交叉耐药性，在某些情况下，对氨基糖苷类药物也有交叉耐药性。用其他药物筛选出的MDR突变体通常仅对氯霉素和氟喹诺酮类药物耐药，不过有两株MDR菌株（如K1385）也对红霉素耐药且对氨基糖苷类药物高度敏感。许多MDR菌株表达了一种分子量约为50 kDa的新型外膜蛋白（OMP），其水平为中度或高度，这是铜绿假单胞菌MDR菌株超表达药物外排系统的典型表型。事实上，这些嗜麦芽窄食单胞菌MDR菌株的50 kDa OMP与抗OprM抗体发生反应，OprM是铜绿假单胞菌MexAB - OprM MDR外排系统的外膜成分。同样，这些MDR菌株的一种约110 kDa的细胞质膜蛋白也与铜绿假单胞菌泵的MexB成分的抗体发生反应。几株嗜麦芽窄食单胞菌临床菌株的外膜和细胞质膜也与抗OprM和抗MexB抗体发生反应。对MDR菌株K1385的50 kDa OMP经溴化氰生成的肽段进行N端氨基酸测序，该肽段被命名为SmeM（嗜麦芽窄食单胞菌多药外排蛋白），结果显示它与铜绿假单胞菌和恶臭假单胞菌的一些外膜多药外排成分非常相似。L1和L2β-内酰胺酶基因的缺失证实这些酶是K1385及其亲本大部分β-内酰胺耐药性的原因。然而，在K1385的L1和L2缺陷衍生物中MDR外排机制的过表达确实使对几种β-内酰胺类药物的耐药性有适度增加。这些数据与MDR外排机制在嗜麦芽窄食单胞菌的多药耐药性中起作用是一致的。
