scholarly journals Differential effects of gram-positive and gram-negative bacterial products on morphine induced inhibition of phagocytosis

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jana Ninkovic ◽  
Vidhu Anand ◽  
Raini Dutta ◽  
Li Zhang ◽  
Anuj Saluja ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Drug Abusers ◽  
Bacterial Clearance ◽  
Chronic Morphine ◽  
Gram Positive ◽  
Bacterial Killing ◽  
Differential Effects ◽  
Secondary Infections ◽  
First Time ◽  
Dependent Signaling Pathway

Abstract Opioid drug abusers have a greater susceptibility to gram positive (Gram (+)) bacterial infections. However, the mechanism underlying opioid modulation of Gram (+) versus Gram (−) bacterial clearance has not been investigated. In this study, we show that opioid treatment resulted in reduced phagocytosis of Gram (+), when compared to Gram (−) bacteria. We further established that LPS priming of chronic morphine treated macrophages leads to potentiated phagocytosis and killing of both Gram (+) and Gram (−) bacteria in a P-38 MAP kinase dependent signaling pathway. In contrast, LTA priming lead to inhibition of both phagocytosis and bacterial killing. This study demonstrates for the first time the differential effects of TLR4 and TLR2 agonists on morphine induced inhibition of phagocytosis. Our results suggest that the incidence and severity of secondary infections with Gram (+) bacteria would be higher in opioid abusers.

scholarly journals Gram-Positive Pneumonia: Possibilities Offered by Phage Therapy

Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1000
Author(s):  
Lucía Fernández ◽  
María Dolores Cima-Cabal ◽  
Ana Catarina Duarte ◽  
Ana Rodríguez ◽  
María del Mar García-Suárez ◽  
...  
Keyword(s):  
Bacterial Pneumonia ◽  
Bacterial Infections ◽  
Pulmonary Infection ◽  
Phage Therapy ◽  
Healthcare Systems ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Main Challenge ◽  
Secondary Infections ◽  
And Staphylococcus Aureus

Pneumonia is an acute pulmonary infection whose high hospitalization and mortality rates can, on occasion, bring healthcare systems to the brink of collapse. Both viral and bacterial pneumonia are uncovering many gaps in our understanding of host–pathogen interactions, and are testing the effectiveness of the currently available antimicrobial strategies. In the case of bacterial pneumonia, the main challenge is antibiotic resistance, which is only expected to increase during the current pandemic due to the widespread use of antibiotics to prevent secondary infections in COVID-19 patients. As a result, alternative therapeutics will be necessary to keep this disease under control. This review evaluates the advantages of phage therapy to treat lung bacterial infections, in particular those caused by the Gram-positive bacteria Streptococcus pneumoniae and Staphylococcus aureus, while also highlighting the regulatory impediments that hamper its clinical use and the difficulties associated with phage research.

scholarly journals Mast cells are critical for controlling the bacterial burden and the healing of infected wounds

2019 ◽  
Vol 116 (41) ◽  
pp. 20500-20504 ◽  
Author(s):  
C. Zimmermann ◽  
D. Troeltzsch ◽  
V. A. Giménez-Rivera ◽  
S. J. Galli ◽  
M. Metz ◽  
...  
Keyword(s):  
Mast Cells ◽  
Wound Infection ◽  
Bacterial Infections ◽  
Wound Closure ◽  
Defense Mechanism ◽  
Defense Responses ◽  
Skin Wound ◽  
Mouse Strains ◽  
Bacterial Clearance ◽  
Bacterial Killing

Skin wound infections are a significant health problem, and antibiotic resistance is on the rise. Mast cells (MCs) have been shown to contribute to host–defense responses in certain bacterial infections, but their role in skin wound superinfection is unknown. We subjected 2 MC-deficient mouse strains to Pseudomonas aeruginosa skin wound infection and found significantly delayed wound closure in infected skin wounds. This delay was associated with impaired bacterial clearance in the absence of MCs. Engraftment of MCs restored both bacterial clearance and wound closure. Bacterial killing was dependent on IL-6 released from MCs, and engraftment with IL-6–deficient MCs failed to control wound infection. Treatment with recombinant IL-6 enhanced bacterial killing and resulted in the control of wound infection and normal wound healing in vivo. Taken together, our results demonstrate a defense mechanism for boosting host innate immune responses, namely effects of MC-derived IL-6 on antimicrobial functions of keratinocytes.

scholarly journals AMPK activates Parkin independent autophagy and improves post sepsis immune defense against secondary bacterial lung infections

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nathaniel B. Bone ◽  
Eugene J. Becker ◽  
Maroof Husain ◽  
Shaoning Jiang ◽  
Anna A. Zmijewska ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Inflammatory Responses ◽  
Abdominal Sepsis ◽  
Immune Defense ◽  
Bacterial Killing ◽  
Lung Infections ◽  
Sepsis Survivors ◽  
The Impact

AbstractMetabolic and bioenergetic plasticity of immune cells is essential for optimal responses to bacterial infections. AMPK and Parkin ubiquitin ligase are known to regulate mitochondrial quality control mitophagy that prevents unwanted inflammatory responses. However, it is not known if this evolutionarily conserved mechanism has been coopted by the host immune defense to eradicate bacterial pathogens and influence post-sepsis immunosuppression. Parkin, AMPK levels, and the effects of AMPK activators were investigated in human leukocytes from sepsis survivors as well as wild type and Park2−/− murine macrophages. In vivo, the impact of AMPK and Parkin was determined in mice subjected to polymicrobial intra-abdominal sepsis and secondary lung bacterial infections. Mice were treated with metformin during established immunosuppression. We showed that bacteria and mitochondria share mechanisms of autophagic killing/clearance triggered by sentinel events that involve depolarization of mitochondria and recruitment of Parkin in macrophages. Parkin-deficient mice/macrophages fail to form phagolysosomes and kill bacteria. This impairment of host defense is seen in the context of sepsis-induced immunosuppression with decreased levels of Parkin. AMPK activators, including metformin, stimulate Parkin-independent autophagy and bacterial killing in leukocytes from post-shock patients and in lungs of sepsis-immunosuppressed mice. Our results support a dual role of Parkin and AMPK in the clearance of dysfunctional mitochondria and killing of pathogenic bacteria, and explain the immunosuppressive phenotype associated Parkin and AMPK deficiency. AMPK activation appeared to be a crucial therapeutic target for the macrophage immunosuppressive phenotype and to reduce severity of secondary bacterial lung infections and respiratory failure.

scholarly journals The antimicrobial potential of cannabidiol

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mark A. T. Blaskovich ◽  
Angela M. Kavanagh ◽  
Alysha G. Elliott ◽  
Bing Zhang ◽  
Soumya Ramu ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Modern Medicine ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
New Class ◽  
Clostridioides Difficile ◽  
Excellent Activity ◽  
Induce Resistance ◽  
First Time

AbstractAntimicrobial resistance threatens the viability of modern medicine, which is largely dependent on the successful prevention and treatment of bacterial infections. Unfortunately, there are few new therapeutics in the clinical pipeline, particularly for Gram-negative bacteria. We now present a detailed evaluation of the antimicrobial activity of cannabidiol, the main non-psychoactive component of cannabis. We confirm previous reports of Gram-positive activity and expand the breadth of pathogens tested, including highly resistant Staphylococcus aureus, Streptococcus pneumoniae, and Clostridioides difficile. Our results demonstrate that cannabidiol has excellent activity against biofilms, little propensity to induce resistance, and topical in vivo efficacy. Multiple mode-of-action studies point to membrane disruption as cannabidiol’s primary mechanism. More importantly, we now report for the first time that cannabidiol can selectively kill a subset of Gram-negative bacteria that includes the ‘urgent threat’ pathogen Neisseria gonorrhoeae. Structure-activity relationship studies demonstrate the potential to advance cannabidiol analogs as a much-needed new class of antibiotics.

Fusogenic porous silicon nanoparticles as a broad-spectrum immunotherapy against bacterial infections

2021 ◽  
Author(s):  
Byungji Kim ◽  
Qinglin Yang ◽  
Leslie W. Chan ◽  
Sangeeta N. Bhatia ◽  
Erkki Ruoslahti ◽  
...  
Keyword(s):  
Porous Silicon ◽  
Broad Spectrum ◽  
Therapeutic Efficacy ◽  
Bacterial Infections ◽  
Silicon Nanoparticles ◽  
First Line ◽  
Gram Positive ◽  
Gram Negative ◽  
Porous Silicon Nanoparticles

RNAi-mediated immunotherapy provided by fusogenic porous silicon nanoparticles demonstrates superior therapeutic efficacy against both Gram-positive and Gram-negative bacterial infections compared with first-line antibiotics.

scholarly journals Salmonella Typhi and Salmonella Paratyphi A elaborate distinct systemic metabolite signatures during enteric fever

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Elin Näsström ◽  
Nga Tran Vu Thieu ◽  
Sabina Dongol ◽  
Abhilasha Karkey ◽  
Phat Voong Vinh ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Bacterial Infections ◽  
Enteric Fever ◽  
Salmonella Typhi ◽  
Two Dimensional ◽  
Flight Mass Spectrometry ◽  
Metabolite Profiles ◽  
Diagnostic Approaches ◽  
First Time

The host–pathogen interactions induced by Salmonella Typhi and Salmonella Paratyphi A during enteric fever are poorly understood. This knowledge gap, and the human restricted nature of these bacteria, limit our understanding of the disease and impede the development of new diagnostic approaches. To investigate metabolite signals associated with enteric fever we performed two dimensional gas chromatography with time-of-flight mass spectrometry (GCxGC/TOFMS) on plasma from patients with S. Typhi and S. Paratyphi A infections and asymptomatic controls, identifying 695 individual metabolite peaks. Applying supervised pattern recognition, we found highly significant and reproducible metabolite profiles separating S. Typhi cases, S. Paratyphi A cases, and controls, calculating that a combination of six metabolites could accurately define the etiological agent. For the first time we show that reproducible and serovar specific systemic biomarkers can be detected during enteric fever. Our work defines several biologically plausible metabolites that can be used to detect enteric fever, and unlocks the potential of this method in diagnosing other systemic bacterial infections.

scholarly journals Antimicrobial Synergy of Silver-Platinum Nanohybrids With Antibiotics

2021 ◽  
Vol 11 ◽  
Author(s):  
Bansi Ranpariya ◽  
Gayatri Salunke ◽  
Srikanta Karmakar ◽  
Kaushik Babiya ◽  
Santosh Sutar ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Bacterial Infections ◽  
Bacterial Biofilm ◽  
Antimicrobial Drugs ◽  
Mortality And Morbidity ◽  
Green Route ◽  
Antimicrobial Synergy ◽  
First Time ◽  
Tuber Extract ◽  
Powerful Strategy

Various bacterial pathogens are responsible for nosocomial infections resulting in critical pathophysiological conditions, mortality, and morbidity. Most of the bacterial infections are associated with biofilm formation, which is resistant to the available antimicrobial drugs. As a result, novel bactericidal agents need to be fabricated, which can effectively combat the biofilm-associated bacterial infections. Herein, for the first time we report the antimicrobial and antibiofilm properties of silver-platinum nanohybrids (AgPtNHs), silver nanoparticles (AgNPs), and platinum nanoparticles (PtNPs) against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The AgPtNHs were synthesized by a green route using Dioscorea bulbifera tuber extract at 100°C for 5 h. The AgPtNHs ranged in size from 20 to 80 nm, with an average of ∼59 nm. AgNPs, PtNPs, and AgPtNHs showed a zeta potential of −14.46, −1.09, and −11.39 mV, respectively. High antimicrobial activity was observed against P. aeruginosa and S. aureus and AgPtNHs exhibited potent antimicrobial synergy in combination with antibiotics such as streptomycin, rifampicin, chloramphenicol, novobiocin, and ampicillin up to variable degrees. Interestingly, AgPtNHs could inhibit bacterial biofilm formation significantly. Hence, co-administration of AgPtNHs and antibiotics may serve as a powerful strategy to treat bacterial infections.

scholarly journals Virus-Induced Changes of the Respiratory Tract Environment Promote Secondary Infections With Streptococcus pneumoniae

2021 ◽  
Vol 11 ◽  
Author(s):  
Vicky Sender ◽  
Karina Hentrich ◽  
Birgitta Henriques-Normark
Keyword(s):  
Immune Response ◽  
Streptococcus Pneumoniae ◽  
Bacterial Infections ◽  
Disease Burden ◽  
Influenza Infection ◽  
Pneumococcal Infection ◽  
Viral Pathogens ◽  
Complex Interactions ◽  
Secondary Infections ◽  
Induced Changes

Secondary bacterial infections enhance the disease burden of influenza infections substantially. Streptococcus pneumoniae (the pneumococcus) plays a major role in the synergism between bacterial and viral pathogens, which is based on complex interactions between the pathogen and the host immune response. Here, we discuss mechanisms that drive the pathogenesis of a secondary pneumococcal infection after an influenza infection with a focus on how pneumococci senses and adapts to the influenza-modified environment. We briefly summarize what is known regarding secondary bacterial infection in relation to COVID-19 and highlight the need to improve our current strategies to prevent and treat viral bacterial coinfections.

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