scholarly journals Bacteriophage adherence to mucus mediates preventive protection against pathogenic bacteria

2019 ◽  
Author(s):  
Gabriel MF Almeida ◽  
Elina Laanto ◽  
Roghaieh Ashrafi ◽  
Lotta-Riina Sundberg

AbstractMetazoan mucosal surfaces are major interfaces between the organism and environment. These surfaces have been proposed to host bacteriophages in a symbiotic relationship with metazoans. Considering the so far poorly understood phage–mucus interaction and its role in ecological interactions and for mucosal bacterial infections, empirical evidence and model systems need to be established. Here, using the fish pathogenFlavobacterium columnareand rainbow trout (Oncorhynchus mykiss), we show that phages infecting the pathogen are capable of binding to primary mucus layers and protecting fish from infections. Furthermore, exposure to mucus changes the bacterial phenotype by increasing bacterial virulence and susceptibility to phage infections. Tests using other phage–bacterium pairs suggest that the relevance of mucus for bacteria and phages may be widespread in the biosphere. Therefore, interactions of bacteria and phages inside the mucus environment may be important for disease and evolution, and this phenomenon has significant potential to be exploited for preventive phage therapy approaches.

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Gabriel M. F. Almeida ◽  
Elina Laanto ◽  
Roghaieh Ashrafi ◽  
Lotta-Riina Sundberg

ABSTRACT Metazoans were proposed to host bacteriophages on their mucosal surfaces in a symbiotic relationship, where phages provide an external immunity against bacterial infections and the metazoans provide phages a medium for interacting with bacteria. However, scarce empirical evidence and model systems have left the phage-mucus interaction poorly understood. Here, we show that phages bind both to porcine mucus and to rainbow trout (Oncorhynchus mykiss) primary mucus, persist up to 7 days in the mucosa, and provide protection against Flavobacterium columnare. Also, exposure to mucus changes the bacterial phenotype by increasing bacterial virulence and susceptibility to phage infections. This trade-off in bacterial virulence reveals ecological benefit of maintaining phages in the metazoan mucosal surfaces. Tests using other phage-bacterium pairs suggest that phage binding to mucus may be widespread in the biosphere, indicating its importance for disease, ecology, and evolution. This phenomenon may have significant potential to be exploited in preventive phage therapy. IMPORTANCE The mucosal surfaces of animals are habitat for microbes, including viruses. Bacteriophages—viruses that infect bacteria—were shown to be able to bind to mucus. This may result in a symbiotic relationship in which phages find bacterial hosts to infect, protecting the mucus-producing animal from bacterial infections in the process. Here, we studied phage binding on mucus and the effect of mucin on phage-bacterium interactions. The significance of our research is in showing that phage adhesion to mucus results in preventive protection against bacterial infections, which will serve as basis for the development of prophylactic phage therapy approaches. Besides, we also reveal that exposure to mucus upregulates bacterial virulence and that this is exploited by phages for infection, adding one additional layer to the metazoan-bacterium-phage biological interactions and ecology. This phenomenon might be widespread in the biosphere and thus crucial for understanding mucosal diseases, their outcome and treatment.


2017 ◽  
Vol 63 (11) ◽  
pp. 865-879 ◽  
Author(s):  
Ayman El-Shibiny ◽  
Salma El-Sahhar

Since their discovery in 1915, bacteriophages have been used to treat bacterial infections in animals and humans because of their unique ability to infect their specific bacterial hosts without affecting other bacterial populations. The research carried out in this field throughout the 20th century, largely in Georgia, part of USSR and Poland, led to the establishment of phage therapy protocols. However, the discovery of penicillin and sulfonamide antibiotics in the Western World during the 1930s was a setback in the advancement of phage therapy. The misuse of antibiotics has reduced their efficacy in controlling pathogens and has led to an increase in the number of antibiotic-resistant bacteria. As an alternative to antibiotics, bacteriophages have become a topic of interest with the emergence of multidrug-resistant bacteria, which are a threat to public health. Recent studies have indicated that bacteriophages can be used indirectly to detect pathogenic bacteria or directly as biocontrol agents. Moreover, they can be used to develop new molecules for clinical applications, vaccine production, drug design, and in the nanomedicine field via phage display.


Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 914
Author(s):  
Heidi M. T. Kunttu ◽  
Anniina Runtuvuori-Salmela ◽  
Mathias Middelboe ◽  
Jason Clark ◽  
Lotta-Riina Sundberg

Viruses of bacteria, bacteriophages, specifically infect their bacterial hosts with minimal effects on the surrounding microbiota. They have the potential to be used in the prevention and treatment of bacterial infections, including in the field of food production. In aquaculture settings, disease-causing bacteria are often transmitted through the water body, providing several applications for phage-based targeting of pathogens, in the rearing environment, and in the fish. We tested delivery of phages by different methods (via baths, in phage-coated material, and via oral delivery in feed) to prevent and treat Flavobacterium columnare infections in rainbow trout fry using three phages (FCOV-S1, FCOV-F2, and FCL-2) and their hosts (FCO-S1, FCO-F2, and B185, respectively). Bath treatments given before bacterial infection and at the onset of the disease symptoms were the most efficient way to prevent F. columnare infections in rainbow trout, possibly due to the external nature of the disease. In a flow-through system, the presence of phage-coated plastic sheets delayed the onset of the disease. The oral administration of phages first increased disease progression, although total mortality was lower at the end of the experiment. When analysed for shelf-life, phage titers remained highest when maintained in bacterial culture media and in sterile lake water. Our results show that successful phage therapy treatment in the aquaculture setting requires optimisation of phage delivery methods in vivo.


2011 ◽  
Vol 77 (21) ◽  
pp. 7868-7872 ◽  
Author(s):  
Elina Laanto ◽  
Lotta-Riina Sundberg ◽  
Jaana K. H. Bamford

ABSTRACTFlavobacteria and their phages were isolated from Finnish freshwaters and fish farms. Emphasis was placed on finding phages infecting the fish pathogenFlavobacterium columnarefor use as phage therapy agents. The host ranges of the flavobacterial phages varied, phages infectingF. columnarebeing more host specific than the other phages.


2004 ◽  
Vol 17 (1) ◽  
pp. 14-56 ◽  
Author(s):  
Herbert Schmidt ◽  
Michael Hensel

SUMMARY In this review, we focus on a group of mobile genetic elements designated pathogenicity islands (PAI). These elements play a pivotal role in the virulence of bacterial pathogens of humans and are also essential for virulence in pathogens of animals and plants. Characteristic molecular features of PAI of important human pathogens and their role in pathogenesis are described. The availability of a large number of genome sequences of pathogenic bacteria and their benign relatives currently offers a unique opportunity for the identification of novel pathogen-specific genomic islands. However, this knowledge has to be complemented by improved model systems for the analysis of virulence functions of bacterial pathogens. PAI apparently have been acquired during the speciation of pathogens from their nonpathogenic or environmental ancestors. The acquisition of PAI not only is an ancient evolutionary event that led to the appearance of bacterial pathogens on a timescale of millions of years but also may represent a mechanism that contributes to the appearance of new pathogens within a human life span. The acquisition of knowledge about PAI, their structure, their mobility, and the pathogenicity factors they encode not only is helpful in gaining a better understanding of bacterial evolution and interactions of pathogens with eukaryotic host cells but also may have important practical implications such as providing delivery systems for vaccination, tools for cell biology, and tools for the development of new strategies for therapy of bacterial infections.


2014 ◽  
Vol 20 (1) ◽  
pp. 43
Author(s):  
Catalina Prada-Peñaranda ◽  
Angela-Victoria Holguin-Moreno ◽  
Andres-Fernando González-Barrios ◽  
Martha-Josefina Vives-Florez

Bacteria easily acquire resistance to antimicrobial agents; this reduces the number of effective antibiotics available to treat bacterial infections. Food contamination by bacteria also generates important economic losses and health risks. Products for human consumption must be free of antibiotics used in clinical treatments, and the control of bacteria with antimicrobials is strictly regulated; however, there is a lack of development of new antibiotics. As a result, the development of new antimicrobial strategies is vital. Viruses that infect bacteria called bacteriophages (phages) have been proposed as an alternative treatment in an approach known as phage-therapy. Several studies have evaluated and demonstrated their effectiveness against pathogenic bacteria; currently, there are private companies dedicated to the development of new products based on phage cocktails, to control some bacterial infections. In Colombia, there is no previous information about the use of phages, but phage-therapy represents a great opportunity to use the diversity of the native microbiota. In this review, we present the perspectives for phage-therapy in Colombia as a treatment against bacterial infections.


2022 ◽  
Vol 23 (2) ◽  
pp. 670
Author(s):  
Nolan Neville ◽  
Nathan Roberge ◽  
Zongchao Jia

Inorganic polyphosphate (polyP) has been implicated in an astonishing array of biological functions, ranging from phosphorus storage to molecular chaperone activity to bacterial virulence. In bacteria, polyP is synthesized by polyphosphate kinase (PPK) enzymes, which are broadly subdivided into two families: PPK1 and PPK2. While both enzyme families are capable of catalyzing polyP synthesis, PPK1s preferentially synthesize polyP from nucleoside triphosphates, and PPK2s preferentially consume polyP to phosphorylate nucleoside mono- or diphosphates. Importantly, many pathogenic bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii encode at least one of each PPK1 and PPK2, suggesting these enzymes may be attractive targets for antibacterial drugs. Although the majority of bacterial polyP studies to date have focused on PPK1s, PPK2 enzymes have also begun to emerge as important regulators of bacterial physiology and downstream virulence. In this review, we specifically examine the contributions of PPK2s to bacterial polyP homeostasis. Beginning with a survey of the structures and functions of biochemically characterized PPK2s, we summarize the roles of PPK2s in the bacterial cell, with a particular emphasis on virulence phenotypes. Furthermore, we outline recent progress on developing drugs that inhibit PPK2 enzymes and discuss this strategy as a novel means of combatting bacterial infections.


Author(s):  
A Runtuvuori-Salmela ◽  
HMT Kunttu ◽  
E Laanto ◽  
GMF Almeida ◽  
K Mäkelä ◽  
...  

SummaryIntensive aquaculture conditions expose fish to bacterial infections, leading to significant financial losses, extensive antibiotic use and risk of antibiotic resistance in target bacteria. Flavobacterium columnare causes columnaris disease in aquaculture worldwide. To develop a bacteriophage-based control of columnaris disease, we isolated and characterized 126 F. columnare strains and 63 phages against F. columnare from Finland and Sweden. Bacterial isolates were virulent on rainbow trout (Oncorhynchus mykiss) and fell into four previously described genetic groups A, C, E and G, with genetic groups C and E being the most virulent. Phage host range studied against a collection of 228 bacterial isolates demonstrated modular infection patterns based on host genetic group. Phages infected contemporary and previously isolated bacterial hosts, but bacteria isolated most recently were generally resistant to previously isolated phages. Despite large differences in geographical origin, isolation year or host range of the phages, whole genome sequencing of 56 phages showed high level of genetic similarity to previously isolated F. columnare phages (Ficleduovirus, Myoviridae). Altogether, this phage collection demonstrates a potential to be used in phage therapy.Significance StatementBacteriophages were discovered already over a century ago, and used widely in treatment of bacterial diseases before the era of antibiotics. Due to harmful effects of antibiotic leakage into environment, aquaculture is a potential target for phage therapy. However, the development of efficient phage therapy approach requires detailed characterization of bacterial pathogen virulence and phage host range. Here, we describe phage-bacterium interactions in the fish pathogen Flavobacterium columnare. We found that genetically similar phages are found from different fish farms, and their infectivity cluster according to genetic group of bacteria. In addition, phages were able to infect bacterial hosts from other farms, which is a preferable trait considering phage therapy approach. However, the most recently isolated phages had broader host range than the previously isolated phages, suggesting a response in the phage community to evolution of resistance in the bacteria. These results show that designing phage therapy for aquaculture (and other) systems needs consideration of both temporal and geographical aspects of the phage-bacterium interaction.


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.


2019 ◽  
Vol 14 (1) ◽  
pp. 28-31 ◽  
Author(s):  
Rowles H. L.

Probiotics are live microorganisms, which when ingested in sufficient amounts, confer health benefits to the host by improving the gut microflora balance. The purpose of this research was to determine whether commercial probiotic products containing multitude of commensal bacteria would reduce the growth rate of pathogenic bacteria, specifically Escherichia coli and Salmonella typhimurium. Growth curves were established, and the growth rates were compared for samples of E. coli, S. typhimurium, Nature’s Bounty Controlled Delivery probiotic, Sundown Naturals Probiotic Balance probiotic, and cocultures of the pathogenic bacteria mixed with the probiotics. The findings of this research were that the commercial probiotics significantly reduced the growth rate of E. coli and S. typhimurium when combined in cocultures. Probiotics containing multiple strains may be taken prophylactically to reduce the risk of bacterial infections caused by E. coli and S. typhimurium. Probiotics could be used to reduce the high global morbidity and mortality rates of diarrheal disease.


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