Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA.
Virulence. 2012 Jul 1;3(4):389-99. doi: 10.4161/viru.20816. Epub 2012 Jun 22.
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.
在军事医疗中心，对伤员的治疗常常因伤口被病原菌定植和感染而变得复杂。这些病原菌包括医院获得性的、常常具有多重耐药性的病原体，如鲍曼不动杆菌-醋酸钙不动杆菌复合体、铜绿假单胞菌和产超广谱β-内酰胺酶的大肠埃希菌和肺炎克雷伯菌。我们在组织培养感染模型中分析了基于多价黏附分子（MAM）7 的宿主细胞抗黏附治疗对上述病原体的疗效。在此，我们观察到，两种重要毒力标志，即黏附性和细胞毒性之间的相关性，可以作为基于 MAM7 抑制细菌感染成功的有用预测指标。最初，我们根据基因型多样性、抗菌药物敏感性和致病性的重要标志（生物膜形成、对培养宿主细胞的黏附和细胞毒性）对 20 个患者分离株（每种病原体 5 个）进行了特征描述。所有分离株均显示出高度的基因型多样性，这也反映了每个病原体组内生物膜形成、黏附和细胞毒性方面的菌株间巨大差异。我们使用表达 MAM7 的非致病性细菌或用重组 MAM7 包被的乳胶珠进行抗黏附治疗，结果显示细胞毒性降低，表明 MAM7 有作为预防剂减轻多重耐药性细菌病原体感染的潜力。
