Longitudinal Surveys Show that Urethral Catheters Harbor Recurrent Polymicrobial Biofilms with Cooperative and Competitive Behaviors Among Cohabitating Pathogens

The analysis of catheter biofilms (CBs) from patients with neurogenic bladder disorders revealed persistent colonization by polymicrobial communities. The recurrence of bacterial species in the CBs of sequentially replaced catheters suggests urothelial reservoirs responsible for recolonization of the catheter surface. Proteomic data for CB samples were indicative of chronic inflammation in the patients’ urinary tracts via neutrophil and eosinophil infiltration and epithelial cell exfoliation. These host defense pathways, effective in killing pathogens during uncomplicated urinary tract infection, failed to eliminate CBs. Intermittent antibiotic drug treatment had different outcomes: either replacement of drug-susceptible by drug-tolerant bacteria or transient microbial biomass reduction followed by resurgence of the previously colonizing bacteria. Proteins that sequester iron and zinc such as lactotransferrin, lipocalin-2 and calprotectin were abundant in the patient’s CBs and urine sediments. Indicative of a host-pathogen battle for bivalent metal ions, acquisition and transport systems for such ions were highly expressed by many organisms residing in CBs. Species part of the Enterococcaceae and Aerococcaceae families, generally not well-characterized in their ability to synthesize siderophores, frequently cohabitated biofilms dominated by siderophore-producing Enterobacteriaceae. In support of metal acquisition cooperativity, we noticed positive abundance correlations for a Proteus mirabilis yersiniabactin-type siderophore system and two Enterococcus faecalis ABC transporters. Distinct bacterial strains highly expressed known or putative cytotoxins that appeared to compromise the survival of co-resident bacteria, e.g. a P. mirabilis hemolysin and Pseudomonas aeruginosa type 6 secretion and pyoverdin biosynthesis systems. In conclusion, there is support for cooperative and competitive behaviors among bacteria cohabitating CBs.

对神经源性膀胱障碍患者的导管生物膜（catheter biofilms, CBs）进行分析后发现，其表面存在持续定殖的多微生物群落。对依次更换导管的CBs中细菌菌种的复现情况进行分析后提示，尿路上皮储库是导致导管表面再次定殖的原因。CB样本的蛋白质组学数据显示，患者尿路存在慢性炎症，表现为中性粒细胞、嗜酸性粒细胞浸润以及上皮细胞脱落。这类在单纯性尿路感染期间可有效杀灭病原体的宿主防御通路，却无法清除CBs。间歇性抗生素治疗呈现出不同结局：要么是药物敏感菌被药物耐受菌取代，要么是微生物生物量短暂减少后，原先定殖的细菌再度复苏。结合铁与锌的蛋白质（如乳铁蛋白（lactotransferrin）、脂质运载蛋白-2（lipocalin-2）以及钙卫蛋白（calprotectin））在患者的CBs与尿液沉渣中含量丰富。这反映出宿主与病原体之间为争夺二价金属离子的竞争：定殖于CBs的诸多微生物均高水平表达此类离子的获取与转运系统。通常在铁载体（siderophores）合成能力方面研究尚不充分的肠球菌科（Enterococcaceae）与气球菌科（Aerococcaceae）菌种，常与以产铁载体的肠杆菌科（Enterobacteriaceae）为优势菌群的生物膜共存。为佐证金属获取的协同性，我们观察到奇异变形杆菌（Proteus mirabilis）的耶尔森杆菌素型铁载体系统与两种粪肠球菌（Enterococcus faecalis）ABC转运蛋白（ABC transporters）的丰度呈显著正相关。不同的细菌菌株可高水平表达已知或推定的细胞毒素，这些毒素似乎会损害共居菌群的存活能力，例如奇异变形杆菌的溶血素、铜绿假单胞菌（Pseudomonas aeruginosa）的6型分泌系统以及脓绿素（pyoverdin）生物合成系统。综上，本研究为共居于CBs的细菌之间同时存在协同与竞争行为提供了证据支持。