HIV Expression in Infected T Cell Clones.

The principal barrier to an HIV-1 cure is the persistence of infected cells harboring replication-competent proviruses despite antiretroviral therapy (ART). HIV-1 transcriptional suppression, referred to as viral latency, is foremost among persistence determinants, as it allows infected cells to evade the cytopathic effects of virion production and killing by cytotoxic T lymphocytes (CTL) and other immune factors. HIV-1 persistence is also governed by cellular proliferation, an innate and essential capacity of CD4+ T cells that both sustains cell populations over time and enables a robust directed response to immunological threats. However, when HIV-1 infects CD4+ T cells, this capacity for proliferation can enable surreptitious HIV-1 propagation without the deleterious effects of viral gene expression in latently infected cells. Over time on ART, the HIV-1 reservoir is shaped by both persistence determinants, with selective forces most often favoring clonally expanded infected cell populations harboring transcriptionally quiescent proviruses. Moreover, if HIV latency is incomplete or sporadically reversed in clonal infected cell populations that are replenished faster than they are depleted, such populations could both persist indefinitely and contribute to low-level persistent viremia during ART and viremic rebound if treatment is withdrawn. In this review, select genetic, epigenetic, cellular, and immunological determinants of viral transcriptional suppression and clonal expansion of HIV-1 reservoir T cells, interdependencies among these determinants, and implications for HIV-1 persistence will be presented and discussed.

An insight into the genome of extensively drug-resistant and uropathogenic Citrobacter werkmanii.

OBJECTIVE: Carbapenemase-producing bacteria pose a serious public-health threat. This study was performed to understand the emergence and genetic features of NDM-producers in hospital setting. METHODS: Samples were collected from a tertiary-care hospital. Isolate identification was performed by 16S rRNA sequencing. The genome of Citrobacter werkmanii (AK-8) was sequenced on an Illumina NextSeq 500 platform. Resistance determinants and pathogenicity islands were determined by ResFinder and PathogenFinder, respectively. MLST, two-component systems and transcription factors were identified by P2RP server, whilst variant calling and insertion sequence (IS) elements were determined by Galaxy and ISfinder, respectively. The genome of AK-8 was compared with uropathogenic Escherichia coli strain 536. RESULTS: This is the first report on whole-genome analysis of extensively drug-resistant NDM-6-producing uropathogenic C. werkmanii ST-104. Resistance genes for all antibiotics except colistin, fosfomycin, fusidic- acid, nitroimidazole, oxazolidinones, tetracycline and glycopeptides were detected in this strain. Genome analysis of AK-8 led to the identification of the BaeSR two-component system regulating production of multidrug efflux proteins. Virulence was regulated by CpxRA, ZraRS, RstAB, UhpAB, AcrAB, RcsBc and UvrY, whereas Bar-UvrY was found to control carbon metabolism, flagellum biosynthesis and biofilm formation. The AK-8 genome encodes 21 chemoreceptors involved in colonisation and pathogenesis. Fur family transcriptional regulator, cAMP receptor protein and RpoS were found to increase the virulence of AK-8. ntBLAST analysis showed 69.60% genetic identity with E. coli 536 as an adaptive feature for survival. CONCLUSION: The emergence of extensively drug-resistant pathogenic C. werkmanii is alarming and it should not be ignored as commensal.

Hospital sewage water: a reservoir for variants of New Delhi metallo-ß-lactamase (NDM)- and extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae.

New Delhi metallo-ß-lactamase (NDM)-producing Enterobacteriaceae have become a threat to public health. Hospital sewage is generally unexplored, having the potential to harbour bacteria causing healthcare-associated infections. Hence, this study was initiated to monitor NDM-producing Enterobacteriaceae in hospital sewage water. A total of 32 isolates with blaNDM variants were detected in hospital sewage water, including 17 Escherichia coli, 8 Citrobacter freundii, 4 Shigella boydii, 2 Citrobacter braakii and 1 Citrobacter farmeri, showing resistance to all antibiotics except colistin. All 32 isolates carried blaNDM (9 blaNDM-1, 11 blaNDM-4, 10 blaNDM-5 and 2 blaNDM-7), 24 isolates carried blaCMY variants (1 blaCMY-2, 3 blaCMY-4, 5 blaCMY-6, 11 blaCMY-42, 2 blaCMY-86 and 2 blaCMY-139), 20 isolates carried blaOXA-type (17 blaOXA-1 and 3 blaOXA-48), 19 isolates carried blaCTX-M and 9 isolates carried ampC on conjugative plasmids of IncFIA, IncFIB, IncFIC, IncP, IncY, IncHI1 and IncI1 types. In E. coli, coexistence of blaNDM-1 with blaCMY-6 and blaCMY-139, of blaNDM-4 with blaCMY-6, blaCMY-42 and blaCMY-86, of blaNDM-5 with blaCMY-6 and blaCMY-42, and of blaNDM-7 with blaCMY-6 was observed. NDM-5-producing S. boydii and NDM-7-producing C. freundii were identified as well as detection of an association of blaNDM-4 and blaOXA-48 in C. braakii and C. farmeri. A class 1 integron was also found on a plasmid. ISAba125 and bleomycin genes were found surrounding all blaNDM variants. The emergence and dissemination of blaNDM variants in hospital sewage water is a matter of concern, creating an endemic scenario leading to the level of an outbreak.

Efficacy of amoxicillin bearing microsphere formulation in treatment of Listeria monocytogenes infection in Swiss albino mice.

The present study deals with the evaluation of the efficacy of amoxicillin bearing poly-lactic-glycolic acid (PLGA) microsphere formulation in treatment of experimental listeriosis in Swiss albino mice. Amoxicillin bearing PLGA microspheres were prepared by water-in-oil-in-water emulsion technique. PLGA microwspheres significantly regulated sustained release of encapsulated drug over extended time period. The rate of release increased in temperature dependent manner. Amoxicillin bearing PLGA microsphere successfully cleared bacterial burdens in vital organs (kidney, spleen, and brain) and also increased survival rate of treated animals in comparison to free form of the drug. The higher efficacy of microsphere based novel formulation of amoxicillin could be attributed to its targeted delivery to infected macrophages as well as sustained release over extended period of time.