Role of anti-inflammatory interleukin 10 in asymptomatic heartworm infection (Dirofilariasis) in dogs

Background: Dirofilaria immitis causes heartworm disease (HWD), a vector-borne zoonotic disease that primarily affects dogs and cats. Occasionally, human beings were reported to be infected as well. The current study aims to discover the asymptomatic dirofilariasis infection in dogs. In addition, to determine the prevalence of heartworm disease and the role of anti-inflammatory interleukin 10 (IL10) in developing the disease. Household dogs were selected from 10 veterinary clinics throughout Basrah, south of Iraq.Methods: The study included 117 dogs older than 12 months, none of them had received heartworm vaccinations, and all of them lived in their owners’ houses for at least 9 months. Animal ethics instructions were followed after the owner’s consent was obtained.  Physical and biochemical examinations were conducted including the examination of circulating antigens of microfilaria. The levels of anti-inflammatory IL10 and pro-inflammatory IL17, IL4, and IFN-γ were measured using ELISA tests. Descriptive statistics were used to evaluate the prevalence and the clinical and immunological results of the study.Results: Canine heartworm disease prevalence was 29.05% (34 out of 117). The physical examination showed normal vital signs for both infected and non-infected dogs. A significant elevation in the total WBC count was noticed in the infected group.  On the other hand, a significant decrease in RBCs count and hemoglobin was found in the infected group. There were neither changes in the platelet count nor the liver enzymes concentration between infected and non-infected groups.  A significant increase in anti-inflammatory interleukin 10 level and a significant decrease in pro-inflammatory IL17, IL4, and IFN-γ were noticed in the infected dogs. Conclusion: It is concluded that dirofilariasis infection is considered to be a serious life-threatening disease for dogs in Iraq. Therefore, a periodic test for heartworm infection every six months is recommended to eradicate heartworm infestations. The infected animals must be treated according to the American Heartworm Association recommendations

Synthesis, Characterization, and Investigation of the Antimicrobial Activity of Cetylpyridinium Tetrachlorozincate

Cetylpyridinium tetrachlorozincate (referred to herein as (CP)2ZnCl4) was synthesized and its solid-state structure was elucidated via single-crystal X-ray diffraction (SC-XRD), revealing a stoichiometry of C42H76Cl4N2Zn with two cetylpyridinium (CP) cations per [ZnCl4]2– tetrahedra. Crystal structures at 100 and 298 K exhibited a zig-zag pattern with alternating alkyl chains and zinc units. The material showed potential for application as a broad-spectrum antimicrobial agent, to reduce volatile sulfur compounds (VSCs) generated by bacteria, and in the fabrication of advanced functional materials. Minimum inhibitory concentration (MIC) of (CP)2ZnCl4 was 60, 6, and 6 μg mL–1 for Salmonella enterica, Staphylococcus aureus, and Streptococcus mutans, respectively. The MIC values of (CP)2ZnCl4 were comparable to that of pure cetylpyridinium chloride (CPC), despite the fact that approximately 16% of the bactericidal CPC is replaced with bacteriostatic ZnCl2 in the structure. A modified layer-by-layer deposition technique was implemented to synthesize mesoporous silica (i.e., SBA-15) loaded with approximately 9.0 wt % CPC and 8.9 wt % Zn

Synthesis, Characterization, and Investigation of the Antimicrobial Activity of Cetylpyridinium Tetrachlorozincate

Cetylpyridinium tetrachlorozincate (referred to herein as (CP)2ZnCl4) was synthesized and its solid-state structure was elucidated via single-crystal X-ray diffraction (SC-XRD), revealing a stoichiometry of C42H76Cl4N2Zn with two cetylpyridinium (CP) cations per [ZnCl4]2– tetrahedra. Crystal structures at 100 and 298 K exhibited a zig-zag pattern with alternating alkyl chains and zinc units. The material showed potential for application as a broad-spectrum antimicrobial agent, to reduce volatile sulfur compounds (VSCs) generated by bacteria, and in the fabrication of advanced functional materials. Minimum inhibitory concentration (MIC) of (CP)2ZnCl4 was 60, 6, and 6 μg mL–1 for Salmonella enterica, Staphylococcus aureus, and Streptococcus mutans, respectively. The MIC values of (CP)2ZnCl4 were comparable to that of pure cetylpyridinium chloride (CPC), despite the fact that approximately 16% of the bactericidal CPC is replaced with bacteriostatic ZnCl2 in the structure. A modified layer-by-layer deposition technique was implemented to synthesize mesoporous silica (i.e., SBA-15) loaded with approximately 9.0 wt % CPC and 8.9 wt % Zn

The SrrAB two-component system regulates Staphylococcus aureus pathogenicity through redox sensitive cysteines

11 pag, 6 figs. Coordinates for the model of SrrB DHp-CA region solved by X-ray crystallography have been deposited in the Protein Data Bank, https://www.rcsb.org/ (ID code 6PAJ). This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1921307117/-/DCSupplemental.Staphylococcus aureus infections can lead to diseases that range from localized skin abscess to life-threatening toxic shock syndrome. The SrrAB two-component system (TCS) is a global regulator of S. aureus virulence and critical for survival under environmental conditions such as hypoxic, oxidative, and nitrosative stress found at sites of infection. Despite the critical role of SrrAB in S. aureus pathogenicity, the mechanism by which the SrrAB TCS senses and responds to these environmental signals remains unknown. Bioinformatics analysis showed that the SrrB histidine kinase contains several domains, including an extracellular Cache domain and a cytoplasmic HAMP-PAS-DHp-CA region. Here, we show that the PAS domain regulates both kinase and phosphatase enzyme activity of SrrB and present the structure of the DHp-CA catalytic core. Importantly, this structure shows a unique intramolecular cysteine disulfide bond in the ATP-binding domain that significantly affects autophosphorylation kinetics. In vitro data show that the redox state of the disulfide bond affects S. aureus biofilm formation and toxic shock syndrome toxin-1 production. Moreover, with the use of the rabbit infective endocarditis model, we demonstrate that the disulfide bond is a critical regulatory element of SrrB function during S. aureus infection. Our data support a model whereby the disulfide bond and PAS domain of SrrB sense and respond to the cellular redox environment to regulate S. aureus survival and pathogenesis.This work was supported by funding from the National Institutes of Health (NIH) and National Institute of Allergy and Infectious Diseases (NIAID) to E.J.F. and P.M.S. (NIAID Grant AI135305). J.M.B. was funded by the NIH (NIAID Grant AI139100-01) and US Department of Agriculture Multistate Reseach Fund (Project NE−1028). W.S.-P. was supported by NIH (NIAID Grant AI134692-03). The J.K.M. lab was supported by the Canadian Institutes of Health Research (Grant PJT-166050). A.M. was supported by grant BIO2016-78571-P from the Ministerio de Economia y Competitividad (Spain).Peer reviewe