Ectonucleotide pyrophosphatase/phosphodiesterase I (ENPP1) was identified several decades ago as a type II transmembrane glycoprotein with nucleotide pyrophosphatase and phosphodiesterase enzymatic activities, critical for purinergic signaling. Recently, ENPP1 has emerged as a critical phosphodiesterase that degrades the stimulator of interferon genes (STING) ligand, cyclic GMP–AMP (cGAMP). cGAMP or analogs thereof have emerged as potent immunostimulatory agents, which have potential applications in immunotherapy. This emerging role of ENPP1 has placed this “old” enzyme at the frontier of immunotherapy. This review highlights the roles played by ENPP1, the mechanism of cGAMP hydrolysis by ENPP1, and small molecule inhibitors of ENPP1 with potential applications in diverse disease states, including cancer.

The staphylococci are implicated in a variety of human infections; however, many clinical microbiology laboratories in Nigeria do not identify staphylococci (in particular coagulase negative staphylococci - CNS) to the species level. Moreover, data from multi-centre assessment on antibiotic resistance and epidemiology of the staphylococci are not available in Nigeria. This study investigated 91 non-duplicate staphylococcal isolates obtained from the microbiology laboratories of eight hospitals in Nigeria during the period January to April 2010.

Background: The burden of healthcare-associated infection (HAI) is 2 to 18 times higher in developing countries. However, few data are available regarding infection prevention and control (IPC) process indicators in these countries. We evaluated hand hygiene (HH) facilities and compliance amongst healthcare workers (HCW) in a 600-bed healthcare facility in Northcentral Nigeria providing tertiary care service for a catchment population of about 20 million. Methods: An in-house facility assessment tool and the World Health Organization (WHO) direct observation method were used to assess the HH facilities and compliance, respectively. Factors associated with good compliance were determined by multivariate analysis. Results: The facility survey was carried out in all 46 clinical units of the hospital. 72% of the units had no poster or written policy on HH; 87% did not have alcohol-based hand rubs; 98% had at least one handwash sink; 28% had flowing tap water all day while 72% utilized cup and bucket; and 58% had no hand drying facilities. A total of 406 HH opportunities were observed among 175 HCWs. The overall compliance was 31%, ranging from 18% among ward attendants to 82% among medical students. Based on WHO “5 moments” for HH, average compliance was 21% before patient contact, 23% before aseptic procedure, 63% after body fluid exposure risk, 41% after patient contact and 40% after contact with patients’ surrounding. Being a medical student was independently associated with high HH compliance, adjusted odds ratio: 13.87 (1.70–112.88). Conclusions: Availability of HH facilities and HCW compliance in a large tertiary hospital in Nigeria is poor. Our findings confirm that HCWs seem more sensitized to their risk of exposure to potential pathogens than to the prevention of HAI cross-transmission. Inadequate HH facilities probably contributed to the poor compliance. Specific measures such as improved facilities, training and monitoring are needed to improve HH compliance.

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE) have been deemed as serious threats by the CDC. Many chronic MRSA and VRE infections are due to biofilm formation. Biofilm are considered to be between 10–10,000 times more resistant to antibiotics, and therefore new chemical entities that inhibit and/or eradicate biofilm formation are needed. Teichoic acids, such as lipoteichoic acids (LTAs) and wall teichoic acids (WTAs), play pivotal roles in Gram-positive bacteria’s ability to grow, replicate, and form biofilms, making the inhibition of these teichoic acids a promising approach to fight infections by biofilm forming bacteria. Here, we describe the potent biofilm inhibition activity against MRSA and VRE biofilms by two LTA biosynthesis inhibitors HSGN-94 and HSGN-189 with MBICs as low as 0.0625 µg/mL against MRSA biofilms and 0.5 µg/mL against VRE biofilms. Additionally, both HSGN-94 and HSGN-189 were shown to potently synergize with the WTA inhibitor Tunicamycin in inhibiting MRSA and VRE biofilm formation.

A cross sectional study of dengue virus infection in febrile patients presumptively diagnosed of malaria in Maiduguri and Jos plateau, Nigeria

A new class of alkynyl isoquinoline antibacterial compounds, synthesized via Sonogashira coupling, with strong bactericidal activity against a plethora of Gram-positive bacteria including methicillin- and vancomycin-resistant Staphylococcus aureus (S. aureus) strains is presented. HSN584 and HSN739, representative compounds in this class, reduce methicillin-resistant S. aureus (MRSA) load in macrophages, whilst vancomycin, a drug of choice for MRSA infections, was unable to clear intracellular MRSA. Additionally, both HSN584 and HSN739 exhibited a low propensity to develop resistance. We utilized comparative global proteomics and macromolecule biosynthesis assays to gain insight into the alkynyl isoquinoline mechanism of action. Our preliminary data show that HSN584 perturb S. aureus cell wall and nucleic acid biosynthesis. The alkynyl isoquinoline moiety is a new scaffold for the development of potent antibacterial agents against fatal multidrug-resistant Gram-positive bacteria.