Mycobacterium Tuberculosis Infection and Inflammation: what is Beneficial for the Host and for the Bacterium?

Tuberculosis is still a major health problem in the world. Initial interactions between Mycobacterium tuberculosis and the host mark the pathway of infection and the subsequent host inflammatory response. This inflammatory response is tightly regulated by both the host and the bacterium during different stages of infection. As infection progresses, the initial intense pro-inflammatory response observed is regulated by suppressive mediators balancing inflammation. In this environment, M. tuberculosis battles to survive interfering with the host inflammatory response. In this review we discuss the major effector molecules involved in inflammation in relation to the different stages of M. tuberculosis infection

Polyphosphate and associated enzymes as global regulators of stress response and virulence in Campylobacter jejuni

Campylobacter jejuni (C. jejuni), a Gram-negative microaerophilic bacterium, is a predominant cause of bacterial foodborne gastroenteritis in humans worldwide. Despite its importance as a major foodborne pathogen, our understanding of the molecular mechanisms underlying C. jejuni stress survival and pathogenesis is limited. Inorganic polyphosphate (poly P) has been shown to play significant roles in bacterial resistance to stress and virulence in many pathogenic bacteria. C. jejuni contains the complete repertoire of enzymes required for poly P metabolism. Recent work in our laboratory and others have demonstrated that poly P controls a plethora of C. jejuni properties that impact its ability to survive in the environment as well as to colonize/infect mammalian hosts. This review article summarizes the current literature on the role of poly P in C. jejuni stress survival and virulence and discusses on how poly P-related enzymes can be exploited for therapeutic/prevention purposes. Additionally, the review article identifies potential areas for future investigation that would enhance our understanding of the role of poly P in C. jejuni and other bacteria, which ultimately would facilitate design of effective therapeutic/preventive strategies to reduce not only the burden of C. jejuni-caused foodborne infections but also of other bacterial infections in humans

Tuberculosis and COVID-19 in the elderly: factors driving a higher burden of disease

Mycobacterium tuberculosis (M.tb) and SARS-CoV-2 are both infections that can lead to severe disease in the lower lung. However, these two infections are caused by very different pathogens (Mycobacterium vs. virus), they have different mechanisms of pathogenesis and immune response, and differ in how long the infection lasts. Despite the differences, SARS-CoV-2 and M.tb share a common feature, which is also frequently observed in other respiratory infections: the burden of disease in the elderly is greater. Here, we discuss possible reasons for the higher burden in older adults, including the effect of co-morbidities, deterioration of the lung environment, auto-immunity, and a reduced antibody response. While the answer is likely to be multifactorial, understanding the main drivers across different infections may allow us to design broader interventions that increase the health-span of older people

The Impact of Aging on the Lung Alveolar Environment, Predetermining Susceptibility to Respiratory Infections

Respiratory infections are one of the top causes of death in the elderly population, displaying susceptibility factors with increasing age that are potentially amenable to interventions. We posit that with increasing age there are predictable tissue-specific changes that prevent the immune system from working effectively in the lung. This mini-review highlights recent evidence for altered local tissue environment factors as we age focusing on increased tissue oxidative stress with associated immune cell changes, likely driven by the byproducts of age-associated inflammatory disease. Potential intervention points are presented

The human macrophage mannose receptor directs Mycobacterium tuberculosis lipoarabinomannan-mediated phagosome biogenesis

Mycobacterium tuberculosis (M.tb) survives in macrophages in part by limiting phagosome–lysosome (P-L) fusion. M.tb mannose-capped lipoarabinomannan (ManLAM) blocks phagosome maturation. The pattern recognition mannose receptor (MR) binds to the ManLAM mannose caps and mediates phagocytosis of bacilli by human macrophages. Using quantitative electron and confocal microscopy, we report that engagement of the MR by ManLAM during the phagocytic process is a key step in limiting P-L fusion. P-L fusion of ManLAM microspheres was significantly reduced in human macrophages and an MR-expressing cell line but not in monocytes that lack the receptor. Moreover, reversal of P-L fusion inhibition occurred with MR blockade. Inhibition of P-L fusion did not occur with entry via Fcγ receptors or dendritic cell–specific intracellular adhesion molecule 3 grabbing nonintegrin, or with phosphatidylinositol-capped lipoarabinomannan. The ManLAM mannose cap structures were necessary in limiting P-L fusion, and the intact molecule was required to maintain this phenotype. Finally, MR blockade during phagocytosis of virulent M.tb led to a reversal of P-L fusion inhibition in human macrophages (84.0 ± 5.1% vs. 38.6 ± 0.6%). Thus, engagement of the MR by ManLAM during the phagocytic process directs M.tb to its initial phagosomal niche, thereby enhancing survival in human macrophages

Tuberculosis Phenotypic and Genotypic Drug Susceptibility Testing and Immunodiagnostics: A Review

Tuberculosis (TB), considered an ancient disease, is still killing one person every 21 seconds. Diagnosis of Mycobacterium tuberculosis (M.tb) still has many challenges, especially in low and middle-income countries with high burden disease rates. Over the last two decades, the amount of drug-resistant (DR)-TB cases has been increasing, from mono-resistant (mainly for isoniazid or rifampicin resistance) to extremely drug resistant TB. DR-TB is problematic to diagnose and treat, and thus, needs more resources to manage it. Together with+ TB clinical symptoms, phenotypic and genotypic diagnosis of TB includes a series of tests that can be used on different specimens to determine if a person has TB, as well as if the M.tb strain+ causing the disease is drug susceptible or resistant. Here, we review and discuss advantages and disadvantages of phenotypic vs. genotypic drug susceptibility testing for DR-TB, advances in TB immunodiagnostics, and propose a call to improve deployable and low-cost TB diagnostic tests to control the DR-TB burden, especially in light of the increase of the global burden of bacterial antimicrobial resistance, and the potentially long term impact of the coronavirus disease 2019 (COVID-19) disruption on TB programs

The UALE project : a cross-sectional approach for trends in HIV/STI prevalence among key populations attending STI clinics in Guatemala

To describe and compare trends in prevalence, sexual behaviour and HIV transmission knowledge data related to sexually transmitted infections (STI) and HIV in patients attending three STI clinics over an 8-year period in Escuintla Department, Guatemala. STI clinic attendees were classified into transmission groups as follows: female sex workers (FSW), men who have sex with men (MSM) and 'high-risk heterosexuals' (HRH). Annual cross-sectional analysis and multivariable Poisson regression adjusted for sociodemographic variables were used for prevalence comparisons and adjusted prevalence trends for HIV/STI outcomes and used for adjusted trends in proportions in sexual behaviour and HIV transmission knowledge outcomes. Endocervical swabs were obtained to detect trichomonas, chlamydia and neisseria infections. Serologies for syphilis and HIV were performed using rapid tests. For reactive HIV samples, positivity was confirmed by an ELISA. All reactive syphilis samples were further confirmed for diagnosis of active syphilis disease. From a total of 4027 clinic attendees, 3213 (79.78%) were FSW, 229 (5.69%) were MSM and 585 (14.53%) were HRH. The proportion of FSW, MSM and HRH who had a single visit was 56.42%, 57.23% and 91.10%, respectively. Overall, HIV prevalence was 2.10% in FSW, 8.17% in MSM and 4.12% in HRH. Prevalence trends in HIV and syphilis decreased in FSW. Prevalence trends in gonorrhoea did not decrease over time neither in FSW nor in HRH. Chlamydia and trichomonas infections in HRH showed an increase prevalence trend. In FSW, trends in condom use in last sexual intercourse with regular and occasional clients were above 93%. FSW show a decreasing trend in HIV, syphilis and chlamydia prevalence. Gonorrhoea prevalence in FSW and HRH did not decrease over time. HRH is a hard to engage population with low follow-up rates and high potential to act as a bridge population

COVID-19 and chronic diabetes: The perfect storm for reactivation TB?

Background: The Coronavirus disease 2019 (COVID-19) pandemic is predicted to have a net negative effect on tuberculosis (TB) control, with an estimated excess of 6.3 million tuberculosis cases and 1.4 million deaths by 2025. Programmatic issues like the lockdown of TB services affect all patients, while biosocial factors have a differential impact on an individual’s risk for TB or adverse TB outcomes. Case presentation: We report three cases of incident TB after resolution of COVID-19 episodes.Coincidently, all cases shared a common risk factor: a chronic history poorly-controlled diabetes. Conclusions: Our findings alert to the threat posed by the synergy between COVID-19 and diabetes, on TB reactivation. In medium- to high-risk settings for TB, we recommend implementation of routine screening for latent TB infection in these cases, and preventive TB treatment in those who are positive. Published version of this presentation: Aguillón-Durán, G.P., Prieto-Martínez, E., Ayala, D. et al. COVID-19 and chronic diabetes: the perfect storm for reactivation tuberculosis?: a case series. J Med Case Reports 15, 621 (2021). https://doi.org/10.1186/s13256-021-03193-