A presentation of culture-positive corneal donors and the effect on clinical outcomes.

PURPOSE: Donor-to-host transmission of infectious agents is a rare but well-recognised complication of corneal transplantation and may carry a grave visual prognosis. In this case series, we describe the clinical features and risk factors of using culture-positive donor corneas for transplantation. METHODS: Retrospective chart review of a series of patients who underwent either penetrating keratoplasty (PK) or Descemet's stripping automated endothelial keratoplasty (DSAEK) with positive microbiology cultivation during routine assessment of donor corneal tissue obtained at the time of surgery. Donor and recipient characteristics, tissue preparation and surgical parameters, clinical signs and outcomes were registered. RESULTS: Eleven patients who received culture-positive corneal grafts were identified: six with Candida, three with Gram-positive bacteria and two with Gram-negative bacteria. Three patients developed clinical keratitis after routine DSAEK using corneas contaminated with Candida species. The median death-to-preservation time (DPT) of these three donor corneas was 18.08 (range 18.08 to 20.90) h, while in the remaining eight donors, it was 12.27 (range 9.32 to 20.47) h. Despite the initiation of antifungal treatment, all three cases required explantation of the graft and a subsequent re-DSAEK. CONCLUSIONS: The use of donor corneas that are culture-positive for Candida carries a risk for developing postoperative keratitis and the risk may be higher in DSAEK. Unlike the cold storage technique employed for donor corneas described in this case series, organ culture technique requires microbiological screening and supplementation of an antifungal agent which may reduce the risk of donor-to-host transmission of fungal infection.

Inflammasomes and Their Role in Innate Immunity of Sexually Transmitted Infections.

Inflammasomes are multiprotein complexes present in the cytosol as pattern recognition receptors or as sensors of damage-associated molecular patterns. After recognition of microbe-associated molecular patterns or host-derived danger signals, nucleotide oligomerization domain-like receptors oligomerize to form inflammasomes. The activation of inflammasomes results in an alarm, which is raised to alert adjacent cells through the processing and release of a number of other substrates present in the cytosol. A wide array of inflammasomes and their adapter molecules have been identified in the host's innate immune system in response to various pathogens. Components of specific pathogens activate different inflammasomes, which once activated in response to pathogen-induced infection, induce the activation of caspases, and the release of mature forms of interleukin-1ß (IL-1ß) and IL-18. Identifying the mechanisms underlying pathogen-induced inflammasome activation is important if we are to develop novel therapeutic strategies to target sexually transmitted infections (STIs) related pathogens. This information is currently lacking in literature. In this review, we have discussed the role of various inflammasomes in sensing different STIs, as well as the beneficial or detrimental effects of inflammasome signaling in host resistance. Additionally, we have discussed both canonical and non-canonical processing of IL-1ß induced with respect to particular infections. Overall, these findings transform our understanding of both the basic biology and clinical relevance of inflammasomes.

Compensatory mutations in agrC partly restore fitness in vitro to peptide deformylase inhibitor-resistant Staphylococcus aureus.

OBJECTIVES: To determine how the fitness cost of deformylase inhibitor resistance conferred by fmt mutations can be genetically compensated. METHODS: Resistant mutants were isolated and characterized with regard to their growth rates in vitro and in neutropenic mice, MIC and DNA sequence. Faster-growing compensated mutants were isolated by serial passage in culture medium, and for a subset of the resistant and compensated mutants whole-genome sequencing was performed. RESULTS: Staphylococcus aureus mutants resistant to the peptide deformylase inhibitor actinonin had mutations in the fmt gene that conferred high-level actinonin resistance and reduced bacterial growth rate. Compensated mutants that remained fully resistant to actinonin and showed increased growth rates appeared within 30-60 generations of growth. Whole-genome sequencing and localized DNA sequencing of mutated candidate genes showed that alterations in the gene agrC were present in the majority of compensated strains. Resistant and compensated mutants grew at similar rates as the wild-type in a mouse thigh infection model. CONCLUSIONS: Resistance to deformylase inhibitors due to fmt mutations reduces bacterial growth rates, but these costs can be reduced by mutations in the agrC gene. Mutants defective in fmt (with or without compensatory agrC mutations) grew well in an animal model, implying that they can also cause infection in a host.