Critical reviews in microbiology
-
Intensive worldwide efforts are underway to determine both the pathogenesis of SARS-CoV-2 infection and the immune responses in COVID-19 patients in order to develop effective therapeutics and vaccines. One type of cell that may contribute to these immune responses is the γδ T lymphocyte, which plays a key role in immunosurveillance of the mucosal and epithelial barriers by rapidly responding to pathogens. Although found in low numbers in blood, γδ T cells consist the majority of tissue-resident T cells and participate in the front line of the host immune defense. ⋯ However, no studies have profoundly investigated these cells in COVID-19 patients to date. γδ T cells can be safely expanded in vivo using existing inexpensive FDA-approved drugs such as bisphosphonate, in order to test its protective immune response to SARS-CoV-2. To support this line of research, we review insights gained from previous coronavirus research, along with recent findings, discussing the potential role of γδ T cells in controlling SARS-CoV-2. We conclude by proposing several strategies to enhance γδ T cell's antiviral function, which may be used in developing therapies for COVID-19.
-
Crit. Rev. Microbiol. · Sep 2019
ReviewmNGS in clinical microbiology laboratories: on the road to maturity.
Metagenomic next-generation sequencing (mNGS) is increasingly being applied in clinical laboratories for unbiased culture-independent diagnosis. Whether it can be a next routine pathogen identification tool has become a topic of concern. We review the current implementation of this new technology for infectious disease diagnostics and discuss the feasibility of transforming mNGS into a routine diagnostic test. ⋯ Although several hurdles, such as workflow validation, quality control, method standardisation, and data interpretation, remain before mNGS can be implemented routinely in clinical laboratories, they are temporary and can be overcome by rapidly evolving technologies. With more validated workflows, lower cost and turnaround time, and simplified interpretation criteria, mNGS will be widely accepted in clinical practice. Overall, mNGS is transforming the landscape of clinical microbiology laboratories, and to ensure that it is properly utilised in clinical diagnosis, both physicians and microbiologists should have a thorough understanding of the power and limitations of this method.
-
Crit. Rev. Microbiol. · May 2018
ReviewEpigenetic regulation in bacterial infections: targeting histone deacetylases.
Pathogens have developed sophisticated strategies to evade the immune response, among which manipulation of host cellular epigenetic mechanisms plays a prominent role. In the last decade, modulation of histone acetylation in host cells has emerged as an efficient strategy of bacterial immune evasion. Virulence factors and metabolic products of pathogenic microorganisms alter expression and activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs) to suppress transcription of host defense genes through epigenetic changes in histone acetylation marks. ⋯ Considerable effort is currently being applied to better understand the effects of HDAC inhibitors on the quality of immune responses to pathogens and to characterize the therapeutic potential of these compounds in microbial infections. In this review, we will discuss the recently discovered mechanisms utilized by bacteria to facilitate their survival within infected hosts through subversion of the host acetylation system and the effects of acetylation modulators, including HDAC inhibitors and bromodomain-containing BET protein inhibitors, on innate immune responses against microbial pathogens. Integration of these two lines of experimental evidence provides critical information on the perspectives of epigenetic therapies targeting protein acetylation in infectious diseases.
-
Crit. Rev. Microbiol. · Mar 2018
ReviewNontypeable Haemophilus influenzae and chronic obstructive pulmonary disease: a review for clinicians.
Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality worldwide. In the lower airways of COPD patients, bacterial infection is a common phenomenon and Haemophilus influenzae is the most commonly identified bacteria. Haemophilus influenzae is divided into typeable and nontypeable (NTHi) strains based on the presence or absence of a polysaccharide capsule. ⋯ Hence, there has been much interest in the development of an effective NTHi vaccine. This review will summarize the current literature concerning the role of NTHi infections in COPD patients and the consequences of using prophylactic antibiotics in patients with COPD. There is particular focus on the rationale, findings of clinical studies and possible future directions of NTHi vaccines in patients with COPD.
-
Crit. Rev. Microbiol. · Sep 2017
ReviewResuscitation-promoting factors are important determinants of the pathophysiology in Mycobacterium tuberculosis infection.
Resuscitation promoting factors (Rpf) are peptidoglycan-hydrolyzing enzymes that are pivotal in the resuscitation of quiescent actinobacteria including Mycobacterium tuberculosis. From the published data, it is clear that Rpf are required for the resuscitation of non-replicating bacilli and pathogenesis in murine infection model of tuberculosis, although their direct influence on human Mycobacterium tuberculosis infection is ill-defined. In this review, we describe the progress in the understanding of the roles that Rpf play in human tuberculosis pathogenesis and importance of bacilli dependent upon Rpf for growth for the outcome of human tuberculosis. We outline how this research is opening up important opportunities for the diagnosis, treatment and prevention of human disease, progress in which is essential to attain the ultimate goal of tuberculosis eradication.