Staphylococcus aureus is a Gram-positive pathogen that causes potentially life-threatening nosocomial- and community-acquired infections, such as osteomyelitis and endocarditis. Staphylococcus aureus has the ability to form multicellular, surface-adherent communities called biofilms, which enables it to survive in various sources of stress, including antibiotics, nutrient limitations, heat shock, and immune responses. Biofilm-forming capacity is now recognized as an important virulence determinant in the development of staphylococcal device-related infections. In light of the projected increase in the numbers of elderly patients who will require semi-permanent indwelling medical devices such as artificial knees and hips, we can anticipate an expanded need for new agents and treatment options to manage biofilm-associated infections in an expanding at-risk population. With better understanding of staphylococcal biofilm formation and growth, novel strategies that target biofilm-associated infections caused by S. aureus have recently been described and seem promising as future anti-biofilm therapies.
Tuberculosis (TB) and human immunodeficiency virus (HIV) infection interfere and impact the pathogenesis phenomena of each other. Owing to atypical clinical presentations and diagnostic complications, HIV/TB co-infection continues to be a menace for healthcare providers. Although the increased access to highly active antiretroviral therapy (HAART) has led to a reduction in HIV-associated opportunistic infections and mortality, the concurrent management of HIV/TB co-infection remains a challenge owing to adverse effects, complex drug interactions, overlapping toxicities and tuberculosis -associated immune reconstitution inflammatory syndrome. Several hypotheses have been put forward for the exacerbation of tuberculosis by HIV and vice versa supported by immunological studies. Discussion on the mechanisms produced by infectious cofactors with impact on disease pathology could shed light on how to design potential interventions that could decelerate disease progression. With no vaccine for HIV and lack of an effective vaccine for tuberculosis, it is essential to design strategies against HIV-TB co-infection.
HIV-1 vaccine functioning relies on successful induction of broadly neutralizing antibodies (bNAbs). CXCR3- circulatory T-follicular helper (cTfh) cells are necessary for inducing B-cells for generating bNAbs. Recent studies have suggested that CXCR3+ Tfh cells might also influence bNAb production. Plasma samples from 34 ART-Naïve HIV-1 infected individuals [long-term nonprogressors (LTNP)-19; Progressors-13] were tested against a heterologous virus panel (n = 11) from subtypes A, B, C, G, AC, BC and AE. Frequencies of CXCR3+ and CXCR3- cTfh-like cells in peripheral circulation were studied using flow cytometry. LTNP showed significantly lower CXCR3+ and higher CXCR3- cTfh-like cell frequencies, while neutralization breadth was observed to be broader in progressors. A positive correlation was observed between bNAb breadth and potency with CXCR3+PD-1+ cTfh-like cells in LTNP. Based on neutralization breadth, 9 HIV-1 infected individuals were classified as 'top neutralizers' and 23 as 'low neutralizers' and they did not show any correlations with CXCR3+ and CXCR3- cTfh-like cells. These preliminary data suggest that CXCR3+ similar to CXCR3- might possess significant functional properties for driving B-cells to produce bNAbs. Hence, an HIV vaccine which is capable of optimal induction of CXCR3+ cTfh cells at germinal centers might confer superior protection against HIV.
The subspecies classification of Mycobacteroides abscessus complex into M. abscessus, M. massiliense and M. bolletii requires the amplification and sequencing of multiple genes. The objective of this study was to evaluate the possibility of subspecies classification using a single PCR target. An in silico study was performed to classify 1613 strains deposited in a public database using 9 genes (partial gene sequences of hsp65, rpoB, sodA, argH, cya, glpK, gnd, and murC, and the full gene sequence of MAB_3542c). We found the housekeeping gene gnd to be able to classify the M. abscessus subspecies with high accuracy (99.94%). A single-gene PCR approach based on gnd would be a suitable replacement for the more expensive, labor-intensive and time-consuming multi-gene PCR analysis currently in use for the subspecies identification of M. abscessus.
Staphylococcus aureus is the leading cause of hospital-acquired infections and can cause a wide range of diseases from mild skin infections to invasive diseases including deep surgical site infections, life-threatening bacteremia, and sepsis. This pathogen remains a challenge to manage due to its ability to rapidly develop resistance to antibiotic treatment and to form biofilms. Despite the current infection control measures which involve mainly antibiotics, the burden of infection remains high. The 'omics' approaches have not led to the discovery of novel antibacterials at a pace sufficient to cope with the emergence of multidrug-resistant and biofilm-forming S. aureus, Hence, new strategies for anti-infective therapies need to be explored urgently. One promising strategy is harnessing the immune response to enhance the protective antimicrobial immunity in the host. This review discusses the potential of monoclonal antibodies and vaccines as alternatives to treat and manage infections caused by planktonic and biofilms of S. aureus.
A vast proportion of coronavirus disease 2019 (COVID-19) individuals remain asymptomatic and can shed severe acute respiratory syndrome (SARS-CoV) type 2 virus to transmit the infection, which also explains the exponential increase in the number of COVID-19 cases globally. Furthermore, the rate of recovery from clinical COVID-19 in certain pockets of the globe is surprisingly high. Based on published reports and available literature, here, we speculated a few immunovirological mechanisms as to why a vast majority of individuals remain asymptomatic similar to exotic animal (bats and pangolins) reservoirs that remain refractile to disease development despite carrying a huge load of diverse insidious viral species, and whether such evolutionary advantage would unveil therapeutic strategies against COVID-19 infection in humans. Understanding the unique mechanisms that exotic animal species employ to achieve viral control, as well as inflammatory regulation, appears to hold key clues to the development of therapeutic versatility against COVID-19.
Acute Undifferentiated Febrile Illness (AUFI) presents a clinical challenge, often characterized by sudden fever, non-specific symptoms, and potential life-threatening implications. This review highlights the global prevalence, types, challenges, and implications of AUFI, especially in tropical and subtropical regions where infectious diseases thrive. It delves into the difficulties in diagnosis, prevalence rates, regional variations, and potential causes, ranging from bacterial and viral infections to zoonotic diseases. Furthermore, it explores treatment strategies, preventive measures, and the critical role of the One Health approach in addressing AUFI. The paper also addresses the emerging zoonotic risks and ongoing outbreaks, including COVID-19, Rickettsia spp., and other novel pathogens, emphasizing their impact on AUFI diagnosis and management. Challenges in resource-limited settings are analyzed, highlighting the need for bolstered healthcare infrastructure, enhanced diagnostics, and collaborative One Health strategies. Amidst the complexity of emerging zoonotic threats, this review underscores the urgency for a multifaceted approach to mitigate the growing burden of AUFI, ensuring early diagnosis, appropriate treatment, and effective prevention strategies.