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Topic Review
ESAT-6 a Major Virulence Factor of Mycobacterium tuberculosis
Mycobacterium tuberculosis (Mtb) virulence relies on its ability to manipulate host macrophages, where it establishes intracellular niches to cross mucosal barriers and avoid pathogen destruction. First, Mtb subverts the endocytic pathway, preventing phagolysosome fusion and proteolytic digestion. Second, it activates innate immune responses to induce its transmigration into the lung parenchyma. There, infected macrophages attract more permissive cells, expanding intracellular niches. Mtb induces the adaptive responses that stimulate its containment and encourage a long life inside granulomas. Finally, the pathogen induces necrotic cell death in macrophages, granuloma destruction, and lung cavitation for transmission. Common to all these events is the major virulence factor: the “early secreted antigenic target of 6 kDa” (ESAT-6, also called EsxA). The loss or gain of mycobacterial virulence is closely linked to the ability of mycobacteria to produce and secrete ESAT-6, and the extension of virulence is correlated with the amount of protein secreted. ESAT-6 secretion from the bacilli requires both the expression of the esx-1 locus for the type VII secretion apparatus and the transcription of both the ESAT-6 gene (esxA) and the culture filtrate protein 10 (CFP-10) gene (esx-B) contained in the RD1 region of the genome. In addition, it requires the protein EspA, which is not encoded in the esx-1 locus but in the extended espACD operon adjacent to RD8. All species and strains deleted in the esx-1 locus, the internal RD1 region, or the esx-1 extended locus espACD exhibit an attenuated phenotype. Mutants with deletions on ESX-1 of Mtb are attenuated in virulence, translating into reduced survival of mycobacteria in cultured macrophages or in experimental animal models of TB. Curiously, the saprophyte species M. smegmatis (Ms) also encodes for an ESX-1 apparatus; however, it does not appear to confer Ms virulence capabilities, as demonstrated by its inability to survive in human macrophages or in amoeba in the environment. Predatory amoeba may have contributed to the evolutionary pressure that selected mycobacterial pathogens for intracellular survival. 
  • 982
  • 25 Jun 2023
Topic Review
Treatment of Invasive Candidiasis
Candida species, belonging to commensal microbial communities in humans, cause opportunistic infections in individuals with impaired immunity. Pathogens encountered in more than 90% cases of invasive candidiasis include C. albicans, C. glabrata, C. krusei, C. tropicalis, and C. parapsilosis. The most frequently diagnosed invasive infection is candidemia. About 50% of candidemia cases result in deep-seated infection due to hematogenous spread. The sensitivity of blood cultures in autopsy-proven invasive candidiasis ranges from 21% to 71%. Non-cultural methods (beta-D-glucan, T2Candida assays), especially beta-D-glucan in combination with procalcitonin, appear promising in the exclusion of invasive candidiasis with high sensitivity (98%) and negative predictive value (95%). There is currently a clear deficiency in approved sensitive and precise diagnostic techniques. Omics technologies seem promising, though require further development and study. Therapeutic options for invasive candidiasis are generally limited to four classes of systemic antifungals (polyenes, antimetabolite 5-fluorocytosine, azoles, echinocandins) with the two latter being highly effective and well-tolerated and hence the most widely used.
  • 982
  • 21 Jun 2022
Topic Review
PPARγ in Brain Viral Infections
Peroxisome Proliferator-Activated Receptor gamma (PPARγ) is a master regulator of metabolism, adipogenesis, inflammation and cell cycle, and it has been extensively studied in the brain in relation to inflammation or neurodegeneration. Specific to viral infections is the ability to subvert signaling pathways of the host cell to ensure virus replication and spreading, as deleterious as the consequences may be for the host.
  • 981
  • 28 Sep 2021
Topic Review
SARS-CoV-2 Infection and Valproic Acid
The histone deacetylase inhibitor valproic acid (VPA) is a potential drug that could be adapted to prevent the progression and complications of SARS-CoV-2 infection. VPA has a history of research in the treatment of various viral infections. VPA inhibits SARS-CoV-2 virus entry, suppresses the pro-inflammatory immune cell and cytokine response to infection, and reduces inflammatory tissue and organ damage by mechanisms that may appear to be sex-related. The antithrombotic, antiplatelet, anti-inflammatory, immunomodulatory, glucose- and testosterone-lowering in blood serum effects of VPA suggest that the drug could be promising for therapy of COVID-19. Sex-related differences in the efficacy of VPA treatment may be significant in developing a personalised treatment strategy for COVID-19.
  • 980
  • 18 May 2022
Topic Review
Nucleic Acid Testing of SARS-CoV-2
The coronavirus disease 2019 (COVID-19) has caused a large global outbreak. It is accordingly important to develop accurate and rapid diagnostic methods. The polymerase chain reaction (PCR)-based method including reverse transcription-polymerase chain reaction (RT-PCR) is the most widely used assay for the detection of SARS-CoV-2 RNA. Along with the RT-PCR method, digital PCR has emerged as a powerful tool to quantify nucleic acid of the virus with high accuracy and sensitivity. Non-PCR based techniques such as reverse transcription loop-mediated isothermal amplification (RT-LAMP) and reverse transcription recombinase polymerase amplification (RT-RPA) are considered to be rapid and simple nucleic acid detection methods and were reviewed in this entry. Non-conventional molecular diagnostic methods including next-generation sequencing (NGS), CRISPR-based assays and nanotechnology are improving the accuracy and sensitivity of COVID-19 diagnosis. 
  • 980
  • 04 Aug 2021
Topic Review
In Silico Strategies in Tuberculosis Drug Discovery
Tuberculosis (TB) remains a serious threat to global public health, responsible for an estimated 1.5 million mortalities in 2018. Discovering new and more potent antibiotics that target novel TB protein targets is an attractive strategy towards controlling the global TB epidemic. In silico strategies can be applied at multiple stages of the drug discovery paradigm to expedite the identification of novel anti-TB therapeutics.
  • 979
  • 29 Dec 2021
Topic Review
Vaccinations of COVID-19
Vaccination has been identified as a critical method of disease control in the context of the current COVID-19 pandemic. This research updated information on vaccine development and to identify areas of concern that require further research. The researchers reviewed the literature on the development of COVID-19 vaccines, their efficacy, and use in special populations, as well as current vaccination strategies. To date, 170 vaccines are in clinical development, with 41 being already approved for use in various countries. The majority of vaccines approved for human use are vector-, subunit-, DNA-, or mRNA-based vaccines, or inactivated viruses. Because of the ongoing mutation of the SARS-CoV-2 virus, well-studied vector vaccines are losing relevance due to the ability of new virus strains to bypass neutralizing antibodies. Simultaneously, PS-based vaccines are becoming more popular. There is mounting evidence that the immunogenicity of COVID-19 vaccines is linked to their clinical efficacy. This has resulted in a shift in vaccination strategies, as well as the use of booster doses and revaccination. Furthermore, vaccination restrictions for children, pregnant women, the elderly, and people with chronic immunosuppressive diseases have been lifted, allowing more people to be vaccinated. New data on vaccine safety, including the incidence of serious adverse events, have been collected. Despite significant advances in the development of and research on COVID-19 vaccines, many questions remain that require further investigation.
  • 977
  • 06 Dec 2022
Topic Review
Inorganic Nanoparticles Carrying Amphotericin B
Amphotericin B is the oldest antifungal molecule which is still currently widely used in clinical practice. Recently, its redox properties (i.e., both prooxidant and antioxidant) have been highlighted in the literature as mechanisms involved in both its activity and its toxicity. Interestingly, similar properties can be described for inorganic nanoparticles. Moreover, in a majority of the published studies, inorganic nanoparticles carrying Amphotericin B are described as having a synergistic activity directly related to the rupture of the redox homeostasis of the pathogen (i.e., fungi, parasites, and yeasts). Consequently, due to the unique properties of inorganic nanoparticles (e.g., magnetism, intrinsic anti-infectious properties, stimuli-triggered responses, etc.), these nanomaterials (i.e., inorganic nanoparticles carrying Amphotericin B) may represent a new generation of medicine that can synergistically enhance the antimicrobial properties of Amphotericin B.
  • 977
  • 24 Oct 2023
Topic Review
Infections Caused by Fungi of the Genus Candida
Colonizing mucous membranes, mainly the oral cavity, intestines, vagina, and skin, fungi of the genus Candida are part of the human microbiota. Vulvovaginal candidiasis (VVC) is one of the most common types of vaginal infections in women around the world and is often underestimated by both patients and doctors. 
  • 976
  • 01 Jun 2022
Topic Review
Mesenchymal Stem Cell Viral Infection and Host Responses
Mesenchymal stem cells (MSCs) play a critical role in response to stress such as infection. They initiate the removal of cell debris, exert major immunoregulatory activities, control pathogens, and lead to a remodeling/scarring phase. Interestingly, many viruses and particularly those associated to chronic infection and inflammation may hijack and polarize MSC’s immune regulatory activities to their own advantages. Virus will remain in the MSC perivascular niche while being protected from immune attack. In the context of immunodepression (e.g. organ transplantation) the hidden viruses may rebound and causing tissue injuries. 
  • 975
  • 01 Aug 2022
Topic Review
Overcome Antibiotic Resistance against Mycobacterium tuberculosis
Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis (Mtb). TB treatment is based on the administration of three major antibiotics: isoniazid, rifampicin, and pyrazinamide. However, multi-drug resistant (MDR) Mtb strains are increasing around the world, thus, allowing TB to spread around the world. The stringent response is demonstrated by Mtb strains in order to survive under hostile circumstances, even including exposure to antibiotics. The stringent response is mediated by alarmones, which regulate bacterial replication, transcription and translation. Moreover, the Mtb cell wall contributes to the mechanism of antibiotic resistance along with efflux pump activation and biofilm formation.
  • 975
  • 01 Nov 2022
Topic Review
Hematologic Malignancies in COVID-19 Pandemic
Obesity is epidemiologically and likely, causally related to various hematological cancers, while both conditions may predispose to severe SARS-CoV-2 infection. The COVID-19 pandemic brought about a variety of obstacles with respect to numerous aspects in the management of hematological malignancies. Patients with hematologic malignancies faced a variety of challenges, pertinent to the nature of an underlying hematologic disorder itself as well as its therapy as a risk factor for severe SARS-CoV-2 infection, suboptimal vaccine efficacy and the need for uninterrupted medical observation and continued therapy. Obesity constitutes another factor which was acknowledged since the early days of the pandemic that predisposed people to severe COVID-19, and shares a likely causal link with the pathogenesis of a broad spectrum of hematologic cancers.
  • 973
  • 25 May 2022
Topic Review
COVID-19-Induced Diabetes
The COVID-19 pandemic has revealed a significant association between SARS-CoV-2 infection and diabetes, whereby individuals with diabetes are more susceptible to severe disease and higher mortality rates. The association between diabetes and COVID-19 is probably bidirectional, recent findings suggest a reciprocal relationship between COVID-19 and diabetes, wherein COVID-19 may contribute to developing new-onset diabetes and worsen existing metabolic abnormalities.
  • 973
  • 08 Aug 2023
Topic Review
Multidrug-Resistant Organisms in LTCF
This entry presents the current knowledge about prevalence and risk factors for colonization by multidrug-resistant organisms (MDRO) in long-term care facilities (LTCF) providing useful references to establish objectives for implementing successful antimicrobial stewardship programs (ASP) that might stop the growing trend of MDRO in this setting. 
  • 971
  • 05 Aug 2021
Topic Review
Antimicrobial Treatment of Pseudomonas aeruginosa Severe Sepsis
Pseudomonas aeruginosa is a pathogen often encountered in a healthcare setting. It has consistently ranked among the most frequent pathogens seen in nosocomial infections, particularly bloodstream and respiratory tract infections. Aside from having intrinsic resistance to many antibiotics, it rapidly acquires resistance to novel agents. Given the high mortality of pseudomonal infections generally, and pseudomonal sepsis particularly, and with the rise of resistant strains, treatment can be very challenging for the clinician.
  • 970
  • 03 Nov 2022
Topic Review
Area under the Concentration-Time Curve-Guided Dosing of Vancomycin
The area under the concentration-time curve (AUC)-guided dosing tended to more strongly decrease the risk of acute kidney injury (AKI) than trough-guided dosing, and a lower risk of treatment failure was demonstrated for higher AUC/minimum inhibitory concentration (MIC) ratios (cut-off of 400). Higher AUCs (cut-off of 600 μg·h/mL) significantly increased the risk of AKI. Although Bayesian estimation with two-point measurement was recommended, the trough concentration alone may be used in patients with mild infections in whom vancomycin (VCM) was administered with q12h. To increase the concentration on days 1–2, the routine use of a loading dose is required. Therapeutic drug monitoring (TDM) on day 2 before steady state is reached should be considered to optimize the dose in patients with serious infections and a high risk of AKI. 
  • 967
  • 28 Mar 2022
Topic Review
COVID-19 and New-Onset Psychosis
Psychosis is a multifactorial condition that typically involves delusions, hallucinations, and disorganized thought, speech or behavior. The observation of an association between infectious epidemics and acute psychosis dates back to the last century. Though infrequently, cases of new-onset psychosis have been observed in patients with COVID-19 since the beginning of the pandemic, leading to concerns that SARS-CoV-2 infection may be associated with an increased risk for the development of psychosis. 
  • 967
  • 31 Jan 2023
Topic Review
Microfluidic Devices for HIV Diagnosis at Point-of-Care Settings
Human immunodeficiency virus (HIV) is a global epidemic; however, many individuals are able to obtain treatment and manage their condition. Progression to acquired immunodeficiency syndrome (AIDS) occurs during late-stage HIV infection, which compromises the immune system, making it susceptible to infections. While there is no cure, antiretroviral therapy can be used provided that detection occurs, preferably during the early phase. However, the detection of HIV is expensive and resource-intensive when tested with conventional methods, such as flow cytometry, polymerase chain reaction (PCR), or enzyme-linked immunosorbent assays (ELISA). Improving disease detection in resource-constrained areas requires equipment that is affordable, portable, and can deliver rapid results. Microfluidic devices have transformed many benchtop techniques to on-chip detection for portable and rapid point-of-care (POC) testing. These devices are cost-effective, sensitive, and rapid and can be used in areas lacking resources. Moreover, their functionality can rival their benchtop counterparts, making them efficient for disease detection.
  • 964
  • 15 Dec 2022
Topic Review
FimH and Anti-Adhesive Therapeutics
Chaperone-usher fimbrial adhesins are powerful weapons against the uropathogens that allow the establishment of urinary tract infections (UTIs). As the antibiotic therapeutic strategy has become less effective in the treatment of uropathogen-related UTIs, the anti-adhesive molecules active against fimbrial adhesins, key determinants of urovirulence, are attractive alternatives. The best-characterized bacterial adhesin is FimH, produced by uropathogenic Escherichia coli (UPEC). Hence, a number of high-affinity mono- and polyvalent mannose-based FimH antagonists, characterized by different bioavailabilities, have been reported. Given that antagonist affinities are firmly associated with the functional heterogeneities of different FimH variants, several FimH inhibitors have been developed using ligand-drug discovery strategies to generate high-affinity molecules for successful anti-adhesion therapy. As clinical trials have shown d-mannose’s efficacy in UTIs prevention, it is supposed that mannosides could be a first-in-class strategy not only for UTIs, but also to combat other Gram-negative bacterial infections. 
  • 962
  • 29 Mar 2022
Topic Review
HIV-Associated Neurocognitive Disorders (HAND)
The chronic infection established by the human immunodeficiency virus 1 (HIV-1) produces serious CD4+ T cell immunodeficiency despite the decrease in HIV-1 ribonucleic acid (RNA) levels and the raised life expectancy of people living with HIV-1 (PLWH) through treatment with combined antiretroviral therapies (cART). HIV-1 enters the central nervous system (CNS), where perivascular macrophages and microglia are infected. Serious neurodegenerative symptoms related to HIV-associated neurocognitive disorders (HAND) are produced by infection of the CNS. Despite advances in the treatment of this infection, HAND significantly contribute to morbidity and mortality globally. 
  • 962
  • 23 Dec 2021
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