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The spirochete Borrelia recurrentis is the causal agent of louse-borne relapsing fever and is transmitted to humans by the infected body louse Pediculus humanus. We have recently demonstrated that the B. recurrentis surface receptor, HcpA, specifically binds factor H, the regulator of the alternative pathway of complement activation, thereby inhibiting complement mediated bacteriolysis. Here, we show that B. recurrentis spirochetes express another potential outer membrane lipoprotein, termed CihC, and acquire C4b-binding protein (C4bp) and human C1 esterase inhibitor (C1-Inh), the major inhibitors of the classical and lectin pathway of complement activation. A highly homologous receptor for C4bp was also found in the African tick-borne relapsing fever spirochete B. duttonii. Upon its binding to B. recurrentis or recombinant CihC, C4bp retains its functional potential, i.e. facilitating the factor I-mediated degradation of C4b. The additional finding that ectopic expression of CihC in serum sensitive B. burgdorferi significantly increased spirochetal resistance against human complement suggests this receptor to substantially contribute, together with other known strategies, to immune evasion of B. recurrentis.

Borrelia recurrentis, the etiologic agent of louse-borne relapsing fever in humans, has evolved strategies, including antigenic variation, to evade immune defence, thereby causing severe diseases with high mortality rates. Here we identify for the first time a multifunctional surface lipoprotein of B. recurrentis, termed HcpA, and demonstrate that it binds human complement regulators, Factor H, CFHR-1, and simultaneously, the host protease plasminogen. Cell surface bound factor H was found to retain its activity and to confer resistance to complement attack. Moreover, ectopic expression of HcpA in a B. burgdorferi B313 strain, deficient in Factor H binding proteins, protected the transformed spirochetes from complement-mediated killing. Furthermore, HcpA-bound plasminogen/plasmin endows B. recurrentis with the potential to resist opsonization and to degrade extracellular matrix components. Together, the present study underscores the high virulence potential of B. recurrentis. The elucidation of the molecular basis underlying the versatile strategies of B. recurrentis to escape innate immunity and to persist in human tissues, including the brain, may help to understand the pathological processes underlying louse-borne relapsing fever.

A central question to biology is how pathogenic bacteria initiate acute or chronic infections. Here we describe a genetic program for cell-fate decision in the opportunistic human pathogen Staphylococcus aureus, which generates the phenotypic bifurcation of the cells into two genetically identical but different cell types during the course of an infection. Whereas one cell type promotes the formation of biofilms that contribute to chronic infections, the second type is planktonic and produces the toxins that contribute to acute bacteremia. We identified a bimodal switch in the agr quorum sensing system that antagonistically regulates the differentiation of these two physiologically distinct cell types. We found that extracellular signals affect the behavior of the agr bimodal switch and modify the size of the specialized subpopulations in specific colonization niches. For instance, magnesium-enriched colonization niches causes magnesium binding to S. aureusteichoic acids and increases bacterial cell wall rigidity. This signal triggers a genetic program that ultimately downregulates the agr bimodal switch. Colonization niches with different magnesium concentrations influence the bimodal system activity, which defines a distinct ratio between these subpopulations; this in turn leads to distinct infection outcomes in vitro and in an in vivo murine infection model. Cell differentiation generates physiological heterogeneity in clonal bacterial infections and helps to determine the distinct infection types.

Objectives With holmium laser enucleation of the prostate (HoLEP) a size‐independent method for surgical treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO) has been introduced. HoLEP offers durable long‐term results with reduced perioperative morbidity. As the risk of disease progression increases with age, the main goals, when offering surgery to an elderly population, are reducing perioperative morbidity and preserving quality of life (QoL). We therefore analyzed the impact of age on outcomes and perioperative morbidity in patients undergoing HoLEP for LUTS at our tertiary referral center. Methods We retrospectively collected data of 487 patients who underwent HoLEP for LUTS secondary to BPO between 2018 and 2019. Patients were divided into group 1 (<70 years), group 2 (70‐79 years), and group 3 (≥80 years). Perioperative parameters, safety, and short‐term functional outcomes were assessed and analyzed. Results Perioperative Clavien‐Dindo grade ≥II complications were seen in 4.1% of patients (20/487). There was no difference in perioperative complications between all age groups (P = .176). Functional outcome was assessed 30 days post surgery. There was significant improvement in median International Prostate Symptom Score of 14, 10, and 8 points for groups 1, 2, and 3 (P < .001), respectively, with constant improvement of median QoL of 3 points for all groups. Median maximum flow rate (Qmax) showed significant improvement of 14.5, 10.5, and 13 mL/s for groups 1 to 3 (P = .467), respectively. Conclusion HoLEP offers acceptable perioperative complication rates even in the oldest patient cohort (≥80 years). Therefore, HoLEP is a safe and efficient option even in oldest patients.