Genes for glycosylphosphatidylinositol toxin biosynthesis in Plasmodium falciparum

About 2.5 million people die of Plasmodium falciparum malaria every year. Fatalities are associated with systemic and organ-specific inflammation initiated by a parasite toxin. Recent studies show that glycosylphosphatidylinositol (GPI) functions as the dominant parasite toxin in the context of infection. GPIs also serve as membrane anchors for several of the most important surface antigens of parasite invasive stages. GPI anchoring is a complex posttranslational modification produced through the coordinated action of a multicomponent biosynthetic pathway. Here we present eight new genes of P. falciparum selected for encoding homologs of proteins essential for GPI synthesis: PIG-A, PIG-B, PIG-M, PIG-O, GPI1, GPI8, GAA-1, and DPM1. We describe the experimentally verified mRNA and predicted amino acid sequences and in situ localization of the gene products to the parasite endoplasmic reticulum. Moreover, we show preliminary evidence for the PIG-L and PIG-C genes. The biosynthetic pathway of the malaria parasite GPI offers potential targets for drug development and may be useful for studying parasite cell biology and the molecular basis for the pathophysiology of parasitic diseases.     

Septic Revision Total Knee Arthroplasty Is Associated With Significantly Higher Mortality Than Aseptic Revisions: Long-Term Single-Center Study (1254 Patients)

BackgroundThe aim of this study is to examine the differences in long-term mortality rates between septic and aseptic revision total knee arthroplasty (rTKA) in a single specialist center over 17-year period.MethodsRetrospective consecutive study of all patients who underwent rTKA at our tertiary center between 2003 and 2019 was carried out. Revisions were classified as septic or aseptic. We identified patients’ age, gender, American Society of Anesthesiologists grade, and body mass index. The primary outcome measure was all-cause mortality at 5 years, 10 years, and over the whole study period of 17 years. Death was identified through both local hospital electronic databases and linked data from the National Joint Registry/NHS Personal Demographic Service. Kaplan-Meier survival curves were used to estimate time to death.ResultsIn total, 1298 consecutive knee revisions were performed on 1254 patients (44 bilateral revisions) with 985 aseptic revisions in 945 patients (75.4%) and 313 septic revisions in 309 patients (24.6%). Average age was 70.6 years (range 27-95) with 720 females (57.4%). Septic revisions had higher mortality rates; patients’ survivorship for septic vs aseptic revisions was 77.6% vs 89.5% at 5 years, 68.7% vs 80.2% at 10 years, and 66.1% vs 75.0% at 17 years; these differences were all statistically significant (P < .0001). The unadjusted 10-year risk ratio of death after septic revision was 1.59 (95% confidence interval 1.29-1.96) compared to aseptic revisions.ConclusionrTKA performed for infection is associated with significantly higher long-term mortality at all time points compared with aseptic revision surgery.Level of EvidenceLevel IV.     

Sex and the nursing home

Despite the known benefits of continued sexual activity on physical, mental, and emotional health, the nursing home resident continues to be sexually invisible. There are so few opportunities where the quality of life can be enhanced so greatly by so basic interventions. Sexuality in the nursing home is one of them. Failure of society to come to grips with the sexual needs of the elderly essentially robs them of a fundamental element of self-worth.     

β-Lactamase Production in Key Gram-Negative Pathogen Isolates from the Arabian Peninsula

SUMMARY

Infections due to Gram-negative bacilli (GNB) are a leading cause of morbidity and mortality worldwide. The extent of antibiotic resistance in GNB in countries of the Gulf Cooperation Council (GCC), namely, Saudi Arabia, United Arab Emirates, Kuwait, Qatar, Oman, and Bahrain, has not been previously reviewed. These countries share a high prevalence of extended-spectrum-β-lactamase (ESBL)- and carbapenemase-producing GNB, most of which are associated with nosocomial infections. Well-known and widespread β-lactamases genes (such as those for CTX-M-15, OXA-48, and NDM-1) have found their way into isolates from the GCC states. However, less common and unique enzymes have also been identified. These include PER-7, GES-11, and PME-1. Several potential risk factors unique to the GCC states may have contributed to the emergence and spread of β-lactamases, including the unnecessary use of antibiotics and the large population of migrant workers, particularly from the Indian subcontinent. It is clear that active surveillance of antimicrobial resistance in the GCC states is urgently needed to address regional interventions that can contain the antimicrobial resistance issue.     

Genetic Contexts of blaNDM-1 in Patients Carrying Multiple NDM-Producing Strains

The carbapenem resistance determinant bla_NDM-1 has been found in various Gram-negative bacteria and upon different plasmid replicon types (Inc). Here, we present four patients within two hospitals in Pakistan harboring between two and four NDM-1-producing Gram-negative bacilli of different species coresident in their stool samples. We characterize the bla_NDM-1 genetic contexts of these 11 NDM-1-producing Gram-negative bacilli in addition to other antimicrobial resistance mechanisms, plasmid replicon profiles, and sequence types (STs) in order to understand the underlying acquisition mechanisms of carbapenem resistance within these bacteria. Two common plasmid types (IncN2 and IncA/C) were identified to carry bla_NDM-1 among the six different bacterial species isolated from the four patients. Two of these strains were novel Citrobacter freundii ST 20 and ST 21. The same IncN2-type bla_NDM-1 genetic context was found in all four patients and within four different species. The IncA/C-type bla_NDM-1 genetic context was found in two different species and in two of the four patients. Combining genetic context characterization with other molecular epidemiology methods, we were able to establish the molecular epidemiological links between genetically unrelated bacterial species by linking their acquisition of an IncN2 or IncA/C plasmid carrying bla_NDM-1 for carbapenem resistance. By combining plasmid characterization and in-depth genetic context assessment, this analysis highlights the importance of plasmids in antimicrobial resistance. It also provides a novel approach for investigating the underlying mechanisms of bla_NDM-1-related spread between bacterial species and genera via plasmids.     

Failure of echinocandin therapy in the treatment of Candida glabrata chorioretinitis

Echinocandins are commonly used as initial empiric therapy in cases of moderate to severe invasive candidiasis. The authors demonstrate that caution should be exercised in applying this approach in certain clinical situations. A case of Candida glabrata fungemia and associated chorioretinitis that was clinically resistant to therapy with micafungin but appeared to resolve with amphotericin B is presented. The authors then briefly review current issues regarding the diagnosis and treatment of C glabrata chorioretinitis.