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 ◽  
...  

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.

Author(s):  
Archana Loganathan ◽  
Prasanth Manohar ◽  
Kandasamy Eniyan ◽  
C. S. VinodKumar ◽  
Sebastian Leptihn ◽  
...  

Abstract Background Antibiotic resistance among pathogenic bacteria has created a global emergency, prompting the hunt for an alternative cure. Bacteriophages were discovered over a century ago and have proven to be a successful replacement during antibiotic treatment failure. This review discusses on the scientific investigation of phage therapy for Gram-positive pathogens and general outlook of phage therapy clinical trials and commercialization. Main body of the abstract This review aimed to highlight the phage therapy in Gram-positive bacteria and the need for phage therapy in the future. Phage therapy to treat Gram-positive bacterial infections is in use for a very long time. However, limited review on the phage efficacy in Gram-positive bacteria exists. The natural efficiency and potency of bacteriophages against bacterial strains have been advantageous amidst the other non-antibiotic agents. The use of phages to treat oral biofilm, skin infection, and recurrent infections caused by Gram-positive bacteria has emerged as a predominant research area in recent years. In addition, the upsurge in research in the area of phage therapy for spore-forming Gram-positive bacteria has added a wealth of information to phage therapy. Short conclusion We conclude that the need of phage as an alternative treatment is obvious in future. However, phage therapy can be used as reserve treatment. This review focuses on the potential use of phage therapy in treating Gram-positive bacterial infections, as well as their therapeutic aspects. Furthermore, we discussed the difficulties in commercializing phage drugs and their problems as a breakthrough medicine.


Crystals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 789
Author(s):  
Shih-Fu Ou ◽  
Ya-Yun Zheng ◽  
Sin-Jen Lee ◽  
Shyi-Tien Chen ◽  
Chien-Hui Wu ◽  
...  

Graphene quantum dots, carbon nanomaterials with excellent fluorescence characteristics, are advantageous for use in biological systems owing to their small size, non-toxicity, and biocompatibility. We used the hydrothermal method to prepare functional N-doped carbon quantum dots (N-CQDs) from 1,3,6-trinitropyrene and analyzed their ability to fluorescently stain various bacteria. Our results showed that N-CQDs stain the cell septa and membrane of the Gram-negative bacteria Escherichia coli, Salmonellaenteritidis, and Vibrio parahaemolyticus and the Gram-positive bacteria Bacillus subtilis, Listeria monocytogenes, and Staphylococcus aureus. The optimal concentration of N-CQDs was approximately 500 ppm for Gram-negative bacteria and 1000 ppm for Gram-positive bacteria, and the exposure times varied with bacteria. N-Doped carbon quantum dots have better light stability and higher photobleaching resistance than the commercially available FM4-64. When excited at two different wavelengths, N-CQDs can emit light of both red and green wavelengths, making them ideal for bioimaging. They can also specifically stain Gram-positive and Gram-negative bacterial cell membranes. We developed an inexpensive, relatively easy, and bio-friendly method to synthesize an N-CQD composite. Additionally, they can serve as a universal bacterial membrane-staining dye, with better photobleaching resistance than commercial dyes.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jana Ninkovic ◽  
Vidhu Anand ◽  
Raini Dutta ◽  
Li Zhang ◽  
Anuj Saluja ◽  
...  

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.


2020 ◽  
Vol 8 (2) ◽  
pp. 191 ◽  
Author(s):  
Despoina Koulenti ◽  
Elena Xu ◽  
Andrew Song ◽  
Isaac Yin Sum Mok ◽  
Drosos E. Karageorgopoulos ◽  
...  

Antimicrobial agents are currently the mainstay of treatment for bacterial infections worldwide. However, due to the increased use of antimicrobials in both human and animal medicine, pathogens have now evolved to possess high levels of multi-drug resistance, leading to the persistence and spread of difficult-to-treat infections. Several current antibacterial agents active against Gram-positive bacteria will be rendered useless in the face of increasing resistance rates. There are several emerging antibiotics under development, some of which have been shown to be more effective with an improved safety profile than current treatment regimens against Gram-positive bacteria. We will extensively discuss these antibiotics under clinical development (phase I-III clinical trials) to combat Gram-positive bacteria, such as Staphylococcus aureus, Enterococcus faecium and Streptococcus pneumoniae. We will delve into the mechanism of actions, microbiological spectrum, and, where available, the pharmacokinetics, safety profile, and efficacy of these drugs, aiming to provide a comprehensive review to the involved stakeholders.


1991 ◽  
Vol 54 (5) ◽  
pp. 360-365 ◽  
Author(s):  
S.J. KNABEL ◽  
H.W. WALKER ◽  
P.A. HARTMAN

A simple well-plate technique was utilized to determine the effect of various metals on the growth of microorganisms in media containing different polyphosphates. Aspergillus flavus and four gram-positive bacteria were completely inhibited by media containing 1% of various alkaline polyphosphates, whereas four gram-negative bacteria were not. Significant differences were observed between the type of polyphosphate added, the type of metal added, and the species of gram-positive bacterium inhibited. The addition of Mg2+ stimulated growth of A. flavus and Bacillus cereus in the presence of tetrasodium pyrophosphate, whereas Mn2+ permitted growth of A. flavus and Staphylococcus aureus in the presence of sodium hexametaphosphate. Iron supplementation allowed the growth of S. aureus and Listeria monocytogenes on media containing 1 % tetrasodium pyrophosphate. A method for determining the amount of calcium and magnesium in water was modified to detect free Mg2+ by replacing EDTA with phosphate. The addition of free Mg2+, but not Mg2+ chelated by tetrasodium pyrophosphate, permitted the growth of B. cereus on a medium containing tetrasodium pyrophosphate. It is speculated that polyphosphates specifically inhibited A. flavus and gram-positive bacteria by removing essential metals from cation-binding sites located within their cell walls.


2018 ◽  
Vol 62 (3) ◽  
pp. 261-267 ◽  
Author(s):  
Agnieszka Pękala-Safińska

AbstractChanges occurring in freshwater ecosystems seem to be fundamental in the development of all microorganisms, including those pathogenic to fish. This has been especially evident in recent years during which dynamic variations in bacterial fish pathology have been observed. Gram-negative bacteria commonly known to be pathogenic to fish, likeAeromonasspp.,Flavobacteriumspp.,Pseudomonasspp., andShewanella putrefaciensare replaced by other species, which until now have not been known to be virulent or even conditionally pathogenic to fish. Nowadays, among these other speciesAcinetobacterspp.,Plesiomonas shigelloides,Sphingomonas paucimobilis, andStenotrophomonas maltophiliaare the most frequently isolated from fish exhibiting clinical signs of disease. Two Gram-positive bacteria have become pathogens of particular importance in fish pathology in Poland:Lactococcus garviaeandStreptococcus iniae. In addition, infections caused by the Gram-positive bacteriumKocuria rhizophilahave appeared in recent years. This bacterium has not been known until now to be pathogenic to fish. Therefore, this infection could be called an emergent disease.


2019 ◽  
Vol 7 (22) ◽  
pp. 3590-3598 ◽  
Author(s):  
Jiajun Qiu ◽  
Wenhao Qian ◽  
Jinkai Zhang ◽  
Dafu Chen ◽  
Kelvin W. K. Yeung ◽  
...  

Minocycline hydrochloride loaded graphene oxide films offer a solution for the issues of insufficient osseointegration and bacterial infections on the implants.


2021 ◽  
Author(s):  
Chaonan Li ◽  
Yite Li ◽  
Qihang Wu ◽  
Tingting Sun ◽  
Zhigang Xie

Bacterial infectious diseases and antimicrobial resistance seriously endanger human health, so alternative therapies for bacterial infections are urgently needed. Recently, photodynamic therapy against bacteria has shown great potential because of...


2020 ◽  
Vol 65 (1) ◽  
pp. e01247-20 ◽  
Author(s):  
Ville Y. P. Väre ◽  
Ryan F. Schneider ◽  
Haein Kim ◽  
Erica Lasek-Nesselquist ◽  
Kathleen A. McDonough ◽  
...  

ABSTRACTBacterial infections and the rise of antibiotic resistance, especially multidrug resistance, have generated a clear need for discovery of novel therapeutics. We demonstrated that a small-molecule drug, PKZ18, targets the T-box mechanism and inhibits bacterial growth. The T-box is a structurally conserved riboswitch-like gene regulator in the 5′ untranslated region (UTR) of numerous essential genes of Gram-positive bacteria. T-boxes are stabilized by cognate, unacylated tRNA ligands, allowing the formation of an antiterminator hairpin in the mRNA that enables transcription of the gene. In the absence of an unacylated cognate tRNA, transcription is halted due to the formation of a thermodynamically more stable terminator hairpin. PKZ18 targets the site of the codon-anticodon interaction of the conserved stem I and reduces T-box-controlled gene expression. Here, we show that novel analogs of PKZ18 have improved MICs, bactericidal effects against methicillin-resistant Staphylococcus aureus (MRSA), and increased efficacy in nutrient-limiting conditions. The analogs have reduced cytotoxicity against eukaryotic cells compared to PKZ18. The PKZ18 analogs acted synergistically with aminoglycosides to significantly enhance the efficacy of the analogs and aminoglycosides, further increasing their therapeutic windows. RNA sequencing showed that the analog PKZ18-22 affects expression of 8 of 12 T-box controlled genes in a statistically significant manner, but not other 5′-UTR regulated genes in MRSA. Very low levels of resistance further support the existence of multiple T-box targets for PKZ18 analogs in the cell. Together, the multiple targets, low resistance, and synergy make PKZ18 analogs promising drugs for development and future clinical applications.


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