The role of microbial interactions in infectious disease

The occurrence of infectious disease is affected by interaction between microorganisms in three ways. The indigenous flora (commensal microorganisms) of some mucous surfaces provide one of the main protective mechanisms against infection by pathogens (disease-producing microbes). The commensal populations interfere with the establishment of pathogens on mucous membranes by evoking anaerobic conditions, by competing for space and nutrients and by producing inhibitors. How, at the beginning of successful infection, pathogens in relatively small numbers overcome this protective activity of the commensal population is unknown. Although not a general phenomenon, some pathogens exacerbate the effects ofothers. The best examples are the potentiation of bacterial infections by existing viral infections: mucosal adherence and penetration by bacteria are enhanced and phagocytic defences against them weakened. Some microorganisms that are unable to produce significant disease on their own may combine with others to cause serious sickness. The harmful effects of these combinations of microorganisms can be explained by the multifactorial nature of pathogenicity (virulence), i.e. the capacity to produce disease. Although each member of the mixed population cannot alone produce the full complement of factors needed for disease production, the complement can be attained by combining contributions from different members.

2021 ◽  
Vol 28 ◽  
Author(s):  
Laura Magnasco ◽  
Chiara Sepulcri ◽  
Roberta Maria Antonello ◽  
Stefano Di Bella ◽  
Laura Labate ◽  
...  

Background: In recent years, many aspects of the physiological role of PCSK9 have been elucidated, particularly regarding its role in lipid metabolism, cardiovascular risk, and its role in innate immunity. Increasing evidence is available about the involvement of PCSK9 in the pathogenesis of viral infections, mainly HCV, and the regulation of host response to bacterial infections, primarily sepsis and septic shock. Moreover, the action of PCSK9 has been investigated as a crucial step in the pathogenesis of malaria infection and disease severity. Objective: This paper aims to review the available published literature on the role of PCSK9 in a wide array of infectious diseases. Conclusion: Besides the ongoing investigation on PCSK9 inhibition among HIV-infected patients to treat HIV- and ART-related hyperlipidemia, preclinical studies indicate how PCSK9 is involved in reducing the replication of HCV. Interestingly, high plasmatic PCSK9 levels have been described in patients with sepsis. Moreover, a protective role of PCSK9 inhibition has also been proposed against dengue and SARS-CoV-2 viral infections. Finally, a loss of function in the PCSK9-encoding gene has been reported to reduce malaria infection mortality.


2021 ◽  
Author(s):  
Dhanalakshmi Menamadathil ◽  
Kajari Das ◽  
Medha Pandya ◽  
Sejal Shah ◽  
Ayushman Gadnayak ◽  
...  

Abstract Furin, a pro-protein convertase, plays a significant role of biological scissor in bacterial, viral, and even mammalian substrates which in turn decides the fate of many viral and bacterial infections along with the numerous ailments caused by cancer, diabetes, inflammations, and neurological disorders. In the wake of the current pandemic caused by the virus SARS COV-2, furin has become the center of attraction for researchers. In the present work, we have searched for novel inhibitors against this interesting human target from FDA-approved antivirals. To enhance the selection of new inhibitors we employed Kohonen’s-artificial neural network-based self-organizing maps for ligand based virtual screening. Promising results were obtained which can help in drug repurposing and network pharmacology studies addressing the errors due to promiscuity/polypharmacology. We found 15 existing FDA antivirals having the potential to inhibit furin. Among these, six compounds have targets on other important human proteins (LDLR, FCGR1A, PCK1, TLR7, DNA and PNP) also. These 15 drugs inhibiting furin could be studied in patients having many viral infections including SARS COV-2, which is known to have many interacting motifs like NSPs, ORFs, and spike protein. We also propose two promising candidate FDA drugs GS-441524 and Grazoprevir (MK-5172) to repurpose as inhibitors of furin. The best results were observed with GS-441524.


Author(s):  
Daisy X. Ji ◽  
Kristen C. Witt ◽  
Dmitri I. Kotov ◽  
Shally R. Margolis ◽  
Alexander Louie ◽  
...  

AbstractType I interferons (IFNs) are essential for anti-viral immunity, but often impair protective immune responses during bacterial infections. How type I IFNs are strongly induced during viral infections, and yet are appropriately restrained during bacterial infections, remains poorly understood. The Super susceptibility to tuberculosis 1 (Sst1) locus in mice confers resistance to many bacterial infections. Here we provide evidence that Sp140 is a gene encoded within the Sst1 locus that functions to repress the expression of type I IFNs during bacterial infections. We generated Sp140−/− mice and find they are susceptible to infection by diverse bacteria, including Listeria monocytogenes, Legionella pneumophila, and Mycobacterium tuberculosis. Susceptibility of Sp140−/− mice to bacterial infection was rescued by crosses to mice lacking the type I IFN receptor (Ifnar−/−). Our results implicate Sp140 as an important repressor of type I IFNs that is essential for resistance to bacterial infections.


2022 ◽  
Vol 12 ◽  
Author(s):  
Aihua Luo ◽  
Fang Wang ◽  
Degang Sun ◽  
Xueyu Liu ◽  
Bingchang Xin

Biofilms, which are essential vectors of bacterial survival, protect microbes from antibiotics and host immune attack and are one of the leading causes that maintain drug-resistant chronic infections. In nature, compared with monomicrobial biofilms, polymicrobial biofilms composed of multispecies bacteria predominate, which means that it is significant to explore the interactions between microorganisms from different kingdoms, species, and strains. Cross-microbial interactions exist during biofilm development, either synergistically or antagonistically. Although research into cross-species biofilms remains at an early stage, in this review, the important mechanisms that are involved in biofilm formation are delineated. Then, recent studies that investigated cross-species cooperation or synergy, competition or antagonism in biofilms, and various components that mediate those interactions will be elaborated. To determine approaches that minimize the harmful effects of biofilms, it is important to understand the interactions between microbial species. The knowledge gained from these investigations has the potential to guide studies into microbial sociality in natural settings and to help in the design of new medicines and therapies to treat bacterial infections.


2019 ◽  
Vol 26 (3) ◽  
pp. 172-182
Author(s):  
Yalda Karimi ◽  
Elizabeth C Giles ◽  
Fatemeh Vahedi ◽  
Marianne V Chew ◽  
Tina Nham ◽  
...  

Type I IFN holds a critical role in host defence, providing protection against pathogenic organisms through coordinating a pro-inflammatory response. Type I IFN provides additional protection through mitigating this inflammatory response, preventing immunopathology. Within the context of viral infections, type I IFN signalling commonly results in successful viral clearance. Conversely, during bacterial infections, the role of type I IFN is less predictable, leading to either detrimental or beneficial outcomes. The factors responsible for the variability in the role of type I IFN remain unclear. Here, we aimed to elucidate differences in the effect of type I IFN signalling on macrophage functioning in the context of TLR activation. Using RAW 264.7 macrophages, we observed the influence of type I IFN to be dependent on the type of TLR ligand, length of TLR exposure and the timing of IFN-β signalling. However, in all conditions, IFN-β increased the production of the anti-inflammatory cytokine IL-10. Examination of RAW 264.7 macrophage function showed type I IFN to induce an activated phenotype by up-regulating MHC II expression and enhancing killing activity. Our results support a context-dependent role for type I IFN in regulating RAW 264.7 macrophage activity.


2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Vladimir Mihailovic ◽  
Jelena S. Katanic Stankovic ◽  
Dragica Selakovic ◽  
Gvozden Rosic

Nanoparticles (NPs) are used in many products and materials for humans such as electronics, in medicine for drug delivery, as biosensors, in biotechnology, and in agriculture, as ingredients in cosmetics and food supplements. Besides that, NPs may display potentially hazardous properties on human health and the environment as a consequence of their abundant use in life nowadays. Hence, there is increased interest of researchers to provide possible therapeutic agents or dietary supplements for the amelioration of NP-induced toxicity. This review summarizes the new findings in the research of the use of antioxidants as supplements for the prevention and alleviation of harmful effects caused by exposure of organisms to NPs. Also, mechanisms involved in the formation of NP-induced oxidative stress and protective mechanisms using different antioxidant substances have also been elaborated. This review also highlights the potential of naturally occurring antioxidants for the enhancement of the antioxidant defense systems in the prevention and mitigation of organism damage caused by NP-induced oxidative stress. Based on the presented results of the most recent studies, it may be concluded that the role of antioxidants in the prevention and treatment of nanoparticle-induced toxicity is unimpeachable. This is particularly important in terms of oxidative stress suppression.


2021 ◽  
Vol 14 (2) ◽  
pp. 087-097
Author(s):  
Shifa Begum ◽  
Tofa Begum ◽  
Naziza Rahman ◽  
Ruhul A. Khan

Antibiotics are widely used most effective medication since the twentieth century against bacterial infections (Tetanus, Strep Throat, Urinary Tract Infections, etc.) and thus save one’s life. Before 20th-century infectious disease played the main role in the death. Thus, antibiotics opened a revolutionary era in the field of medication. These cannot fight against viral infections. Antibiotics are also known as an antibacterial that kill or slow down bacterial growth and prohibit the bacteria to harm. Resistance comes as a curse with antibiotics that occurs when bacteria change in some way that reduces or eliminates the effectiveness of drugs, chemicals or other agents designed to cure or prevent infections. It is now a significant threat to public health that is affecting humans worldwide outside the environment of the hospital. When a bacterium once become resistant to antibiotic then the bacterial infections cannot be cured with that antibiotic. Thus, the emergence of antibiotic-resistance among the most important bacterial pathogens causing more harm. In this context, the classification of antibiotics, mode of action of antibiotics, and mechanism of resistance and the process of overcoming antibiotic resistance are discussed broadly.


2021 ◽  
Vol 9 ◽  
Author(s):  
Jesús Chávez-Reyes ◽  
Carlos E. Escárcega-González ◽  
Erika Chavira-Suárez ◽  
Angel León-Buitimea ◽  
Priscila Vázquez-León ◽  
...  

Uncontrolled diabetes results in several metabolic alterations including hyperglycemia. Indeed, several preclinical and clinical studies have suggested that this condition may induce susceptibility and the development of more aggressive infectious diseases, especially those caused by some bacteria (including Chlamydophila pneumoniae, Haemophilus influenzae, and Streptococcus pneumoniae, among others) and viruses [such as coronavirus 2 (CoV2), Influenza A virus, Hepatitis B, etc.]. Although the precise mechanisms that link glycemia to the exacerbated infections remain elusive, hyperglycemia is known to induce a wide array of changes in the immune system activity, including alterations in: (i) the microenvironment of immune cells (e.g., pH, blood viscosity and other biochemical parameters); (ii) the supply of energy to infectious bacteria; (iii) the inflammatory response; and (iv) oxidative stress as a result of bacterial proliferative metabolism. Consistent with this evidence, some bacterial infections are typical (and/or have a worse prognosis) in patients with hypercaloric diets and a stressful lifestyle (conditions that promote hyperglycemic episodes). On this basis, the present review is particularly focused on: (i) the role of diabetes in the development of some bacterial and viral infections by analyzing preclinical and clinical findings; (ii) discussing the possible mechanisms by which hyperglycemia may increase the susceptibility for developing infections; and (iii) further understanding the impact of hyperglycemia on the immune system.


2019 ◽  
pp. 189-211
Author(s):  
Leah Bauer ◽  
Carolyn Chooljian ◽  
Whitney Johnson

Generalized complaints such as fever, chills, malaise, and body aches are common presentations to the emergency department (ED). Some of these are due to viral infections, and some are due to systemic bacterial infections. Clues to the specific infection can be found in the geographic location of the patient or the patient’s exposure to wildlife (e.g., ticks) and animals. The patient’s history and the timing of the illness play an important part in helping to identify the possible source or cause of the infection. This chapter presents questions related to the diagnosis, clinical effects, and most appropriate treatment of a wide range of these systemic infectious disease emergencies.


Author(s):  
Chantal Simon ◽  
Hazel Everitt ◽  
Françoise van Dorp ◽  
Nazia Hussain ◽  
Emma Nash ◽  
...  

This chapter in the Oxford Handbook of General Practice explores infectious disease in general practice. It covers immunization and symptoms, signs, and notification of infectious disease. It explores sepsis, illness in returning travellers, and immunocompromise. It also examines childhood viral infections, staphylococcal and streptococcal infection, and other bacterial infections.


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