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Central venous catheters (CVCs) represent a significant source of infection in patients undergoing hematopoietic stem cell transplantation and can add to the cost of care, morbidity, and mortality. Organisms forming biofilms on the inner surface of catheters require a much higher local antibiotic concentration to clear the pathogen growth. Antibiotic lock therapy (ALT) represents one such strategy to achieve such high intraluminal concentrations of antibiotics and can facilitate catheter salvage. Patients with catheter colonization (CC) or hemodynamically stable catheter‐related bloodstream infection (CRBSI) received ALT per institutional policy. We analyzed the incidence of CC and CRBSI and salvage rate of tunneled CVCs (Hickman) with ALT in patients undergoing hematopoietic stem cell transplant in this retrospective study. Catheter colonization was noted in 9.8% and CRBSI in 10.7% patients. Gram‐negative bacilli (GNB) accounted for 45% and 83% of isolates in CC and CRBSI, respectively. In patients with CRBSI, the rate of catheter salvage with the use of ALT in addition to systemic antibiotics was 86% compared to 55% in patients with systemic antibiotics use only (P = 0.06). There was no CRBSI related mortality, and no increase in resistant strains was noted at subsequent CRBSI. In conclusion, ALT represents an important strategy for catheter salvage, especially for gram‐negative infections, in a carefully selected patient population.

Invasion of human erythrocytes by Plasmodium falciparum merozoites involves multiple interactions between host receptors and their merozoite ligands. Here we report human Cyclophilin B as a receptor for PfRhopH3 during merozoite invasion. Localization and binding studies show that Cyclophilin B is present on the erythrocytes and binds strongly to merozoites. We demonstrate that PfRhopH3 binds to the RBCs and their treatment with Cyclosporin A prevents merozoite invasion. We also show a multi-protein complex involving Cyclophilin B and Basigin, as well as PfRhopH3 and PfRh5 that aids the invasion. Furthermore, we report identification of a de novo peptide CDP3 that binds Cyclophilin B and blocks invasion by up to 80%. Collectively, our data provide evidence of compounded interactions between host receptors and merozoite surface proteins and paves the way for developing peptide and small-molecules that inhibit the protein−protein interactions, individually or in toto, leading to abrogation of the invasion process.

Edited by Gerald W. HartToxoplasma gondii is a ubiquitous, obligate intracellular eukaryotic parasite that causes congenital birth defects, disease in immunocompromised individuals, and blindness. Protein glycosylation plays an important role in the infectivity and evasion of immune responses of many eukaryotic parasites and is also of great relevance to vaccine design. Here we demonstrate that micronemal protein 2 (MIC2), a motility-associated adhesin of T. gondii, has highly glycosylated thrombospondin repeat (TSR) domains. Using affinity-purified MIC2 and MS/MS analysis along with enzymatic digestion assays, we observed that at least seven C-linked and three O-linked glycosylation sites exist within MIC2, with >95% occupancy at these O-glycosylation sites. We found that addition of O-glycans to MIC2 is mediated by a protein O-fucosyltransferase 2 homolog (TgPOFUT2) encoded by the TGGT1_273550 gene. Even though POFUT2 homologs are important for stabilizing motility-associated adhesins and for host infection in other apicomplexan parasites, loss of TgPOFUT2 in T. gondii had only a modest impact on MIC2 levels and the wider parasite proteome. Consistent with this, both plaque formation and tachyzoite invasion were broadly similar in the presence or absence of TgPOFUT2. These findings indicate that TgPOFUT2 O-glycosylates MIC2 and that this glycan, in contrast to previous findings in another study, is dispensable in T. gondii tachyzoites and for T. gondii infectivity.

Hemoglobin degradation/hemozoin formation, essential steps in the Plasmodium life cycle, are targets of existing antimalarials. The pathway still offers vast possibilities to be explored for new antimalarial discoveries. Here, we characterize heme detoxification protein, PfHDP, a major protein involved in hemozoin formation, as a novel drug target. Using in silico and biochemical approaches, we identified two heme binding sites and a hemoglobin binding site in PfHDP. Treatment of Plasmodium falciparum 3D7 parasites with peptide corresponding to the hemoglobin binding domain in PfHDP resulted in food vacuole abnormalities similar to that seen with a cysteine protease inhibitor, E-64 (I-1). Screening of compounds that bound the modeled PfHDP structure in the heme/hemoglobin-binding pockets from Maybridge Screening Collection identified a compound, ML-2, that inhibited parasite growth in a dose-dependent manner, thus paving the way for testing its potential as a new drug candidate. These results provide functional insights into the role of PfHDP in Hz formation and further suggest that PfHDP could be an important drug target to combat malaria.

Despite availability of effective treatments for nicotine addiction, smoking remains prevalent with serious health consequences. Most smokers recognize the ill effects of smoking but are unable to quit. Nicotine addiction may be viewed as any other chronic illness that results from exposure to a recognizable agent (tobacco) and manifests with a well-documented set of signs and symptoms. Much like any chronic disease, both environmental and genetic factors determine the occurrence and severity of this affliction. There has been recent focus on uncovering the genetic basis of nicotine addiction. In this article, we have attempted to briefly review the current evidence for the role of genetics in smoking as well as comment on available pharmacotherapeutic options for treating nicotine dependence.

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