Inoculum and Route Variation as Determinants of Fatality Outcome and Metabolomic Fingerprints in Local Strain of Methicillin‐Resistant Staphylococcus aureus (MRSA) Infection
Authors: Pilau Nicholas Nathaniel , Sani Yusuf , Aliyu Muhammad Aminu , Ibrahim Lawal , Ajayi Victoria 
Published: June 2021

We investigated putative determinants of relative abundance and localization of pathogen, types and patterns of pathogen‐borne metabolomic changes in hosts using various but commonly documented route in Methicillin‐Resistant Staphylococcus aureus (MRSA) infection in mammals. This was done to measure contribution of varying strain inoculum as well as route of infection to mortality in clinical scenarios modeled using mouse infection. Inherent in this research was to test suggestive proportional relationship between size of pathogen inoculum with severity of symptoms and intensity of gross lesions in tissues. A total of twenty‐seven mice were used for the study, they were allocated into three groups: Intraperitonial, Intranasal and Oral with three replicates: 1010; 108 and 105. Pathogen inoculum was varied using serial dilution of culture suspension concentrated by centrifuging at 8000g for 20minutes until 1010CFU achieved. Serial dilution made using miliQ water (Gibco) from 1010 to100. Confirmation for pathogen strain done using complement of culture and microscopy, sensitivity to methicillin and 16S Sanger sequencing data, MRSA local strain was used for the study. After acclimation, each mice group was infected with varied inoculum and presenting symptoms documented. Most infected replicates became moribund in about a week to ten days for all groups. Samples of blood and urine collected each day post infection for hemogram using auto hematology analyser and cyanmethemoglobin absorbance analysis and urinalysis. Samples of trachea, stomach, liver, spleen and kidneys collected immediately after death for culture isolation and histopathology studies. The result showed MRSA infection caused broad ranges of hemodynamic changes, notably marked lymphopenia, macrocytic anemia and thrombocytopenia which was statistically significant (P<0.05), clinical signs and symptoms were similar for all groups but vary in severity. Pathogen was differentially localized in different organs. This outcome was greatly influenced by dose of inoculum as the 105 replicate were minimally symptomatic and had lesser pathogen abundance. Route of infection was a determinant as the orally infected replicate showed the most severe presentation. Lesions produced following histopathology indicate an established pattern with severity depending on inoculum dose but not as much of varied route. Most organs showed marked lymphopenia and thickened alveolar wall with interstitial edema in all replicates. The broad pattern established in this study has clinical application of early recognition and predictability index in MRSA infection, with hope that a better understanding of hemodynamics and modulators of pathogen abundance will translate in improvement of treatment protocol to reduce mortality.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.