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Kimani, J.

Publications and source records attributed to Kimani, J..

3 recordsLinked to original sources
bioRxiv2022

Antimicrobial resistance and virulence characteristics of Klebsiella pneumoniae isolates in Kenya

Klebsiella pneumoniae is a globally significant opportunistic pathogen causing healthcare-associated and community-acquired infections. This study examined the epidemiology and the distribution of resistance and virulence genes in clinical K. pneumoniae strains in Kenya. Eighty-nine K. pneumoniae isolates were collected over six years from five counties in Kenya and were analyzed using whole genome sequencing and bioinformatics. These isolates were obtained from community-acquired (62/89) and healthcare-associated infections (21/89), and the hospital environment (6/89). Genetic analysis revealed the presence of blaNDM-1 and blaOXA-181 carbapenemase genes and the armA and rmtF genes known to confer pan-aminoglycoside resistance. The most abundant extended-spectrum beta-lactamase genes identified were blaCTX-M-15 (36/89), blaTEM (35/89), and blaOXA (18/89). In addition, one isolate had a mobile colistin resistance gene (mcr-8). Fluoroquinolone resistance-conferring mutations in gyrA and parC genes were also observed. The most notable virulence factors were those associated with hyper-virulence (rmpA/A2 and magA), yersiniabactin (ybt), salmochelin (iro), and aerobactin (iuc and iutA). Thirty-eight distinct sequence types were identified, including known global lineages ST14, ST15, ST147, and ST307, and a regional clone ST17 implicated in regional outbreaks. In addition, this study genetically characterized two potential hypervirulent isolates and two community-acquired ST147 high-risk clones that contained carbapenemase genes, yersiniabactin, and other multidrug resistance genes. These results demonstrate that the resistome and virulome of Kenyan clinical and hospital environmental K. pneumoniae isolates are diverse. The reservoir of high risk-clones capable of spreading resistance and virulence factors have the potential to cause unmanageable infection outbreaks with high morbidity and mortality. AUTHOR SUMMARYKlebsiella pneumoniae is one of the human-disease-causing bacteria that easily acquires and spreads antibiotic resistance genes and is thus a serious threat to human health. We studied both the antibiotic resistance genes and the genes it uses to cause disease (virulence). Forty-two percent of our isolates were multidrug resistant (MDR). They carried several resistance and virulence genes bound in mobile circular DNA molecules called plasmids which easily migrate and spread the genes between bacteria. We identified 38 distinct K. pneumoniae strains (STs) distributed within the study sites. Fifteen isolates were classified under the groups of K. pneumoniae strains known to cause global infection outbreaks such as ST14, ST15 and ST147 collected from Nairobi and Kisumu, hotspot areas for spread of resistance. In particular, two ST147 isolates were resistant to carbapenems and one isolate to colistin, which are last line antibiotics. We also identified two isolates with the potential to cause high levels of disease. We concluded that the presence of highly resistant and virulent strains in the hospital and community demonstrates a need for the continuous monitoring and management of MDR K. pneumoniae infections to prevent disease outbreaks that are difficult to control and that lead to high death rate.

microbiology↗
bioRxiv2021

Endocervical regulatory T cells are associated with decreased genital inflammation and lower HIV target cell abundance

Regulatory T cells (Tregs) play important roles in tissue homeostasis, but few studies have investigated tissue Tregs in the context of genital inflammation, HIV target cell density, and vaginal microbiota in humans. In women from Nairobi (n=64), the proportion of CD4+ CD25+ CD127low Tregs in the endocervix correlated with those in blood (r=0.31, p=0.01), with a higher Treg frequency observed in the endocervix (median 3.8 vs 2.0%, p<0.0001). Most Tregs expressed FoxP3 in both compartments, and CTLA-4 expression was higher on endocervical Tregs compared to blood (median 50.8 vs 6.0%, p<0.0001). More than half (34/62, 55%) of participants displayed a non-Lactobacillus dominant vaginal microbiota, which was not associated with endocervical Tregs or CD4+ T cell abundance. In a multivariable linear regression, endocervical Treg proportions were inversely associated with the number of elevated pro-inflammatory cytokines (p=0.03). Inverse Treg associations were also observed for specific cytokines including IL-1{beta}, G-CSF, Eotaxin, IL-1RA, IL-8, and MIP-1 {beta}. Higher endocervical Treg proportions were associated with lower abundance of endocervical CD4+ T cells (0.30 log10 CD4+ T cells per log10 Treg, p=0.00028), with a similar trend for Th17 cells (p=0.09). Selectively increasing endocervical Tregs may represent a pathway to reduce genital tract inflammation in women.

immunology↗
bioRxiv2018

Medroxyprogesterone acetate mediated alteration in the vaginal microbiota and microenvironment in a Kenyan sex worker cohort

AbstractThe hormonal contraceptive Medroxyprogesterone Acetate (MPA) is associated with increased risk of Human Immunodeficiency Virus (HIV), via incompletely understood mechanisms. Increased diversity in the vaginal microbiota modulates genital inflammation and is associated with increased HIV-1 acquisition. However, the effect of MPA on diversity of the vaginal microbiota is relatively unknown. In a cohort of female Kenyan sex workers, negative for sexually transmitted infections (STIs), with Nugent Scores <7 (N=58 of 370 screened), MPA correlated with significantly increased diversity of the vaginal microbiota as assessed by 16S rRNA gene sequencing. MPA was also significantly associated with low vaginal glycogen and -amylase, factors implicated in vaginal colonization by lactobacilli, bacteria believed to protect against STIs. Furthermore, increased diversity of the vaginal microbiota correlated with activation of vaginal HIV-1 target cells. Results were recapitulated in humanized mice where MPA treatment was associated with increased diversity of the vaginal microbiota, low glycogen, and enhanced HIV-1 susceptibility. Together these results suggest MPA-induced hypo-estrogenism may alter key metabolic components necessary for vaginal colonization by certain bacterial species including lactobacilli, and allow for greater bacterial diversity in the vaginal microbiota. Bacterial diversity in the vaginal microbiota correlates with activation of HIV-1 target cells, which might thus contribute to enhanced susceptibility to HIV-1.

molecular biology↗