Biology subjects

Ali, H.

Publications and source records attributed to Ali, H..

4 recordsLinked to original sources

bioRxiv2018

Mycoplasma genitalium incidence, persistence, concordance between partners and progression: systematic review and meta-analysis

BackgroundMycoplasma genitalium is increasingly seen as an emerging sexually transmitted pathogen, and has been likened to Chlamydia trachomatis, but its natural history is poorly understood. The objectives of this systematic review were to determine M. genitalium incidence, persistence, concordance between sexual partners, and the risk of pelvic inflammatory disease (PID).\n\nMethodsWe searched Medline, EMBASE, LILACS, IndMed and African Index Medicus from 1 January 1981 until 17 March 2018. Two independent researchers screened studies for inclusion and extracted data. We examined results in forest plots, assessed heterogeneity and conducted meta-analysis where appropriate. Risk of bias was assessed for all studies.\n\nResultsWe screened 4634 records and included 17 studies; five (4100 women) reported on incidence, five (636 women) on persistence, 10 (1346 women and men) on concordance and three (5139 women) on PID. Incidence in women in two very highly developed countries was 1.07 per 100 person-years (95% CI, 0.61 to 1.53, I2 0%). Median persistence of M. genitalium was estimated from one to three months in four studies but 15 months in one study. In ten studies measuring M. genitalium infection status in couples, 39-50% of male or female sexual partners of infected participants also had M. genitalium detected. In prospective studies, the incidence of PID was higher in women with M. genitalium than those without (RR 1.68, 95% CI 0.59 to 2.77, I2 0%, 2 studies).\n\nDiscussionBased on findings from this and our linked review of prevalence, concordant M. genitalium might be less common than for C. trachomatis and the age distributions of the infections differ. The synthesised data about prevalence, incidence and persistence of M. genitalium infection are inconsistent. Taken together with evidence about antimicrobial resistance in the two infections, M. genitalium is not the new chlamydia.\n\nRegistration NumbersPROSPERO: CRD42015020420, CRD42015020405\n\nKEY MESSAGESO_LIThere are calls for widespread screening for Mycoplasma genitalium, but the natural history of this emerging sexually transmitted pathogen is poorly understood.\nC_LIO_LIM. genitalium incidence was 1.07 (95% confidence intervals, CI 0.61 to 1.53) per 100-person years in women in highly developed countries, 39-50% of infected individuals had a heterosexual partner with M. genitalium and the risk ratio for pelvic inflammatory disease was 1.68 (95% CI 0.59 to 2.77).\nC_LIO_LIThe duration of untreated M. genitalium infection is probably longer than persistent detection of M. genitalium, as measured in most cohort studies, in which inadvertent treatment cannot be ruled out.\nC_LIO_LIThe results of this systematic review and other evidence sources show important differences in the epidemiology and dynamics of M. genitalium and Chlamydia trachomatis infection.\nC_LI

epidemiology↗

bioRxiv2018

Parallel evolution of frog antimicrobial peptides produces identical conformations but subtly distinct membrane and antibacterial activities

Frogs such as Rana temporaria and Litoria aurea secrete numerous closely related antimicrobial peptides (AMPs) as an effective chemical dermal defence. Despite the high similarity in physical properties and preference for adopting secondary amphipathic, -helix conformations in membrane mimicking milieu, their spectrum of activity and potency often varies considerably. Damage or penetration of the bacterial plasma membrane is considered essential for AMP activity and hence distinguishing apparently similar AMPs according to their behaviour in, and effects on, model membranes will inform understanding of species specific effective antimicrobial mechanisms. Here we use a combination of molecular dynamics simulations, circular dichroism and patch-clamp to investigate the basis for differing anti-bacterial activities in representative AMPs from each species; temporin L and aurein 2.5. Despite adopting near identical, -helix conformations in the steady-state in a variety of membrane models, these two AMPs can be distinguished both in vitro and in silico based on their dynamic interactions with model membranes; the greater conformational flexibility and the higher amplitude channel conductance induced offers a rationale for the greater potency and broader spectrum of activity of temporin L over aurein 2.5. Specific contributions from individual residues are identified that define the mechanisms of action of each AMP. Our findings suggest AMPs in frogs are examples of parallel evolution whose utility is based on apparently similar but subtly distinct mechanisms of action.

biophysics↗

bioRxiv2018

Minor sequence modifications in temporin B cause drastic changes in antibacterial potency and selectivity by fundamentally altering membrane activity

Antimicrobial peptides (AMPs) are a potential source of new molecules to counter the increase in antimicrobial resistant infections but a better understanding of their properties is required to understand their native function and for effective translation as therapeutics. Details of the mechanism of their interaction with the bacterial plasma membrane are desired since damage or penetration of this structure is considered essential for AMP activity. Relatively modest modifications to AMP primary sequence can induce substantial changes in potency and/or spectrum of activity but, hitherto, have not been predicted to substantially alter the mechanism of interaction with the bacterial plasma membrane. Here we use a combination of molecular dynamics simulations, circular dichroism, solid-state NMR and patch clamp to investigate the extent to which temporin B and its analogues can be distinguished both in vitro and in silico on the basis of their interactions with model membranes. Enhancing the hydrophobicity of the N-terminus and cationicity of the C-terminus in temporin B improves its membrane activity and potency against both Gram-negative and Gram-positive bacteria. In contrast, enhancing the cationicity of the N-terminus abrogates its ability to trigger channel conductance and renders it ineffective against Staphylococcus aureus while nevertheless enhancing its potency against Escherichia coli. Our findings suggest even closely related AMPs may target the same bacterium with fundamentally differing mechanisms of action.

biophysics↗

bioRxiv2017

Prevalence of Mycoplasma genitalium in different population groups: systematic review and meta-analysis

BackgroundMycoplasma genitalium is a common cause of non-gonococcal non-chlamydial urethritis and cervicitis. Testing of asymptomatic populations has been proposed, but prevalence rates in asymptomatic populations are not well established. We aimed to estimate the prevalence of M. genitalium in adults in the general population, in clinic-based samples, pregnant women, men who have sex with men (MSM) and female sex workers (FSW).\n\nMethodsWe searched Embase, Medline, IndMED, AIM and LILACS from 1 January 1991 to 12 July 2016 without language restrictions. We included studies with 500 participants or more. We screened and selected studies and extracted data in duplicate. We examined eligible studies in forest plots and conducted random effects meta-analysis to estimate prevalence, if appropriate. Between study heterogeneity was examined using the I2 statistic and meta-regression.\n\nResultsOf 3,316 screened records, 63 were included. In randomly selected samples from the general population, the summary prevalence estimate was 1.3% (95% confidence intervals, CI 1.0 to 1.8%, I2 41.5%, 3 studies) in countries with higher levels of development and 3.9% (95% CI 2.2 to 6.7, I2 89.2%, 3 studies) in countries with lower levels. Prevalence estimates were similar in women and men (p=0.47). In clinic-based samples prevalence estimates were higher, except in asymptomatic patients (0.8%, 95% CI 0.4 to 1.4, I2 0.0%, 3 studies). Summary prevalence estimates were: pregnant women 0.9% (95% CI 0.6 to 1.4%, I2 0%, 4 studies); MSM in the community 3.2% (95% CI 2.1 to 5.1, I2 78.3%, 5 studies); FSW in the community 15.9% (95% CI 13.5 to 18.9, I2 =79.9%, 4 studies).\n\nDiscussionThis systematic review can inform testing guidelines for M. genitalium infection. The low estimated prevalence of M. genitalium in the general population, pregnant women and asymptomatic attenders at clinics does not support expansion of testing to asymptomatic people in these groups.\n\nRegistration Numbers\n\nPROSPERO: CRD42015020420

epidemiology↗