Activation of cellular responses by cyclic dinucleotides and lipopolysaccharide: a proteomic study on gingival fibroblasts.

Background: Bacterial cyclic dinucleotides (CDNs), cyclic di-guanosine monophosphate (c-di-GMP), and cyclic di-adenosine monophosphate (c-di-AMP) upregulate interferon signaling proteins of human gingival fibroblasts (HGFs). However, the simultaneous effect of bacterial CDNs and lipopolysaccharides (LPS) on the HGF proteome is unknown.

Aim: The aim was to apply an unbiased proteomics approach to evaluate how simultaneous exposure to CDNs and (Pg) LPS affect the global proteome of HGFs.

The utilization of an unconventional approach to introduce basic bacteriology in a medical school bridge program.

Bacteria form an intense portion of reading and learning for students enrolled in microbiology education. As a part of the foundational course outline of bacteriology, bacterial classification is a significant topic of discussion. The purpose of our study was to analyze whether bacterial classification can be taught with a phylogenetic tree approach that might be more engaging and beneficial to student learners of microbiology.

Alternative first-line malaria treatment.

Malaria is a disease affecting millions of people, especially in Africa, Asia, and South America, and has become a substantial economic burden. Because malaria is contracted through the bite of a mosquito vector, it is very challenging to prevent. Bed nets and insect repellents are used in some homes; others do not have or use them even when available.

Detection of CTX-M and SHV Genes in Extended Spectrum Beta-Lactamase Producing Klebsiella Pneumoniae and Pseudomonas Aeruginosa in a Tertiary Hospital in North-central Nigeria.

Background: Antimicrobial resistance (AMR) is an emerging threat to global health security. Globally, an estimated 700,000 deaths are attributed to AMR annually. Annual deaths due to AMR are projected to reach 10 million by 2050 if current trends persist.

Proteomic and phosphoproteomic analyses of Jurkat T-cell treated with 2'3' cGAMP reveals various signaling axes impacted by cyclic dinucleotides.

Cyclic dinucleotides (CDNs), such as 2'3'-cGAMP, bind to STING to trigger the production of cytokines and interferons, mainly via activation of TBK1. STING activation by CDN also leads to the release and activation of Nuclear Factor Kappa-light-chain-enhancer of activated B cells (NF-κB) via the phosphorylation of Inhibitor of NF-κB (IκB)-alpha (IκBα) by IκB Kinase (IKK). Beyond the canonical TBK1 or IKK phosphorylations, little is known about how CDNs broadly affect the phosphoproteome and/or other signaling axes.

Re-sensitization of Multidrug-Resistant and Colistin-Resistant Gram-Negative Bacteria to Colistin by Povarov/Doebner-Derived Compounds.

Colistin, typically viewed as the antibiotic of last resort to treat infections caused by multidrug-resistant (MDR) Gram-negative bacteria, had fallen out of favor due to toxicity issues. The recent increase in clinical usage of colistin has resulted in colistin-resistant isolates becoming more common. To counter this threat, we have investigated previously reported compounds, and , and developed 13 compounds with more desirable drug-like properties for colistin sensitization against 16 colistin-resistant bacterial strains, three of which harbor the plasmid-borne mobile colistin resistance ().

Isoquinoline Antimicrobial Agent: Activity against Intracellular Bacteria and Effect on Global Bacterial Proteome.

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 strains is presented. HSN584 and HSN739, representative compounds in this class, reduce methicillin-resistant (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.

Membrane acting Povarov-Doebner derived compounds potently disperse preformed multidrug resistant Gram-positive bacterial biofilms.

The National Institute of Health (NIH) estimates that the majority of human microbial infections are either linked to or directly caused by bacterial biofilms and these infections are immune to most currently approved FDA drugs. Hence, there is a need for the development of potent antibiotics against biofilms. We have previously shown that pentafluorosulfanyl (SF)-containing quinoline compounds, which were synthesized via the Povarov reaction, kill persister bacteria (Onyedibe et al.

Mechanistic Studies and Efficacy of an Oxadiazole-Containing Antibiotic.

Methicillin-resistant (MRSA) infections are still difficult to treat, despite the availability of many FDA-approved antibiotics. Thus, new compound scaffolds are still needed to treat MRSA. The oxadiazole-containing compound, , has been shown to reduce lipoteichoic acid (LTA) in , but the mechanism that accounts for LTA biosynthesis inhibition remains uncharacterized.

Comparative Studies to Uncover Mechanisms of Action of -(1,3,4-Oxadiazol-2-yl)benzamide Containing Antibacterial Agents.

Drug-resistant bacterial pathogens still cause high levels of mortality annually despite the availability of many antibiotics. Methicillin-resistant (MRSA) is especially problematic, and the rise in resistance to front-line treatments like vancomycin and linezolid calls for new chemical modalities to treat chronic and relapsing MRSA infections. Halogenated -(1,3,4-oxadiazol-2-yl)benzamides are an interesting class of antimicrobial agents, which have been described by multiple groups to be effective against different bacterial pathogens.

Global proteomics of fibroblast cells treated with bacterial cyclic dinucleotides, c-di-GMP and c-di-AMP.

Background: Constant exposure of human gingival fibroblasts (HGFs) to oral pathogens trigger selective immune responses. Recently, the activation of immune response to cyclic dinucleotides (CDNs) via STING has come to the forefront. Reports show that other proteins outside the STING-TBK1-IRF3 axis respond to CDNs but a global view of impacted proteome in diverse cells is lacking.

SF- and SCF-substituted tetrahydroquinoline compounds as potent bactericidal agents against multidrug-resistant persister Gram-positive bacteria.

Bacteria persister cells are immune to most antibiotics and hence compounds that are active against persister bacteria are needed. We screened a chemical library of SF- and SCF-substituted tetrahydroquinoline compounds, synthesized the Povarov reaction, for antibacterial activity and identified active compounds that displayed good activities against many Gram-positive bacteria, including persisters. The most potent of these compounds, , inhibited the growth of drug-resistant Gram-positive bacterial pathogens (including clinical strains) at concentrations ranging from 1 μg mL to 4 μg mL.

Erratum to: Mortality attributable to third-generation cephalosporin resistance in Gram-negative bloodstream infections in African hospitals: a multi-site retrospective study.

[This corrects the article DOI: 10.1093/jacamr/dlaa130.].

Mortality attributable to third-generation cephalosporin resistance in Gram-negative bloodstream infections in African hospitals: a multi-site retrospective study.

Background: Bloodstream infections (BSI) caused by Enterobacteriaceae show increasing frequency of resistance to third-generation cephalosporin (3GC) antibiotics on the African continent but the mortality impact has not been quantified.

Methods: We used historic data from six African hospitals to assess the impact of 3GC resistance on clinical outcomes in and BSI. We matched each bacteraemic patient to two uninfected patients.

Lipoteichoic Acid Biosynthesis Inhibitors as Potent Inhibitors of and Growth and Biofilm Formation.

Methicillin-resistant (MRSA) and vancomycin-resistant (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.

Global Proteomic Analyses of STING-Positive and -Negative Macrophages Reveal STING and Non-STING Differentially Regulated Cellular and Molecular Pathways.

Purpose: Cyclic guanosine monophosphate-adenosine monophosphate and other bacterial-derived cyclic di-guanosine monophosphate or cyclic di-adenosine monophosphate trigger innate immune responses through binding to stimulator of interferon genes (STING). Thus in chronic infection, such as in periodontitis, immune cells can be exposed to bacterial DNA and/or cyclic dinucleotides, potentially activating STING to cause inflammation. Thus far the cyclic GMP-AMP synthase-STING- TANK-binding kinase 1 pathway has been well characterized but a global perspective of how the presence or lack of STING affect the proteome is lacking.

Assessment of hand hygiene facilities and staff compliance in a large tertiary health care facility in northern Nigeria: a cross sectional study.

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.

Potent trifluoromethoxy, trifluoromethylsulfonyl, trifluoromethylthio and pentafluorosulfanyl containing (1,3,4-oxadiazol-2-yl)benzamides against drug-resistant Gram-positive bacteria.

According to the Centers for Disease Control and Prevention (CDC), methicillin-resistant (MRSA) affects about 80 000 patients in the US annually and directly causes about 11 000 deaths. Therefore, despite the fact that there are several drugs available for the treatment of MRSA, there is a need for new chemical entities. We previously reported that 1,3,4-oxadiazolyl sulfonamide was bacteriostatic and inhibited MRSA strains with a minimum inhibitory concentration (MIC) of 2 μg mL.

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

Background: In Nigeria, where malaria is endemic, greater than 70% of febrile illnesses are treated presumptively as malaria, often without a laboratory evaluation for other possible causes of fever. This cross-sectional study evaluated the presence of dengue virus infection in febrile patients, presumptively diagnosed of malaria infections in the clinic.

Methodology: Blood samples were collected from 529 febrile patients (246 in Jos and 283 in Maiduguri) attending the general outpatient clinics of the Jos University Teaching Hospital (JUTH) and the University of Maiduguri Teaching Hospital (UMTH) and tested for anti-dengue immunoglobulin M (IgM) and immunoglobulin G (IgG), as well as anti-non-structural protein (NS1) by ELISA.

ENPP1, an Old Enzyme with New Functions, and Small Molecule Inhibitors-A STING in the Tale of ENPP1.

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.

Inhibitors of Intracellular Gram-Positive Bacterial Growth Synthesized via Povarov-Doebner Reactions.

can survive both inside and outside of phagocytic and nonphagocytic host cells. Once in the intracellular milieu, most antibiotics have reduced ability to kill , thus resulting in relapse of infection. Consequently, there is a need for antibacterial agents that can accumulate to lethal concentrations within host cells to clear intracellular infections.

Hand hygiene knowledge, training and practice: A cross-sectional study in a tertiary health institution, North-central Nigeria.

Background: Hand hygiene (HH) is the single most important means of preventing hospital-acquired infections. We set out to determine the knowledge, training gaps, and practice of HH in a tertiary health institution in a resource constrained setting.

Methods: This cross-sectional study was conducted among health care workers in a 600-bed capacity tertiary health centre.

Proteomic analysis of bacterial response to a 4-hydroxybenzylidene indolinone compound, which re-sensitizes bacteria to traditional antibiotics.

Halogenated 4-hydroxybenzylidene indolinones have been shown to re-sensitize methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE) to methicillin and vancomycin respectively. The mechanism of antibiotic re-sensitization was however not previously studied. Here, we probe the scope of antibiotic re-sensitization and present the global proteomics analysis of S.

larvae in the urine of a patient with transitional cell carcinoma of the bladder: a case report.

Disseminated infection with refers to the massive migration of infective larvae from the gastrointestinal tract to other organs that are not involved in the normal life cycle of the parasite. We describe the case of a Nigerian male with transitional cell carcinoma of the bladder in whom larvae of was identified in the urine. This report involves a 60-year old male Nigerian presenting to the Urology clinic of the Jos University teaching hospital, Nigeria with disseminated The index patient presented with a 5 month history of total haematuria, urinary frequency, urgency, nocturia, straining to pass urine, feeling of incomplete voiding and terminal dribbling.

Lassa Fever 2016 Outbreak in Plateau State, Nigeria-The Changing Epidemiology and Clinical Presentation.

Lassa fever (LF) outbreaks in Nigeria mostly occur in rural areas and during the dry season, peaking between December through February. Fever is a cardinal presenting feature among the myriad manifestations of LF. Thirty four patients with clinical diagnosis of LF were analyzed.