scholarly journals Exploring Mucin as Adjunct to Phage Therapy

2021 ◽  
Vol 9 (3) ◽  
pp. 509
Author(s):  
Amanda Carroll-Portillo ◽  
Henry C. Lin
Keyword(s):  
Pathogenic Bacteria ◽  
Structural Changes ◽  
Phage Therapy ◽  
Bacterial Species ◽  
Gi Tract ◽  
Beneficial Bacteria ◽  
Phage Cocktail ◽  
Small Intestinal ◽  
Gastrointestinal Dysbiosis

Conventional phage therapy using bacteriophages (phages) for specific targeting of pathogenic bacteria is not always useful as a therapeutic for gastrointestinal (GI) dysfunction. Complex dysbiotic GI disorders such as small intestinal bowel overgrowth (SIBO), ulcerative colitis (UC), or Crohn’s disease (CD) are even more difficult to treat as these conditions have shifts in multiple populations of bacteria within the microbiome. Such community-level structural changes in the gut microbiota may require an alternative to conventional phage therapy such as fecal virome transfer or a phage cocktail capable of targeting multiple bacterial species. Additionally, manipulation of the GI microenvironment may enhance beneficial bacteria–phage interactions during treatment. Mucin, produced along the entire length of the GI tract to protect the underlying mucosa, is a prominent contributor to the GI microenvironment and may facilitate bacteria–phage interactions in multiple ways, potentially serving as an adjunct during phage therapy. In this review, we will describe what is known about the role of mucin within the GI tract and how its facilitation of bacteria–phage interactions should be considered in any effort directed at optimizing effectiveness of a phage therapy for gastrointestinal dysbiosis.

scholarly journals hfqPlays Important Roles in Virulence and Stress Adaptation in Cronobacter sakazakii ATCC 29544

2015 ◽  
Vol 83 (5) ◽  
pp. 2089-2098 ◽  
Author(s):  
Seongok Kim ◽  
Hyelyeon Hwang ◽  
Kwang-Pyo Kim ◽  
Hyunjin Yoon ◽  
Dong-Hyun Kang ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Soft Agar ◽  
Host Cells ◽  
Neonatal Meningitis ◽  
Animal Cells ◽  
Content Type ◽  
Flagellar Biosynthesis

Cronobacterspp. are opportunistic pathogens that cause neonatal meningitis and sepsis with high mortality in neonates. Despite the peril associated withCronobacterinfection, the mechanisms of pathogenesis are still being unraveled. Hfq, which is known as an RNA chaperone, participates in the interaction with bacterial small RNAs (sRNAs) to regulate posttranscriptionally the expression of various genes. Recent studies have demonstrated that Hfq contributes to the pathogenesis of numerous species of bacteria, and its roles are varied between bacterial species. Here, we tried to elucidate the role of Hfq inC. sakazakiivirulence. In the absence ofhfq,C. sakazakiiwas highly attenuated in disseminationin vivo, showed defects in invasion (3-fold) into animal cells and survival (103-fold) within host cells, and exhibited low resistance to hydrogen peroxide (102-fold). Remarkably, the loss ofhfqled to hypermotility on soft agar, which is contrary to what has been observed in other pathogenic bacteria. The hyperflagellated bacteria were likely to be attributable to the increased transcription of genes associated with flagellar biosynthesis in a strain lackinghfq. Together, these data strongly suggest thathfqplays important roles in the virulence ofC. sakazakiiby participating in the regulation of multiple genes.

scholarly journals An Insight into the Role of Benefical Bacteria in Periodontal Pocket Recolonization: A Literature Review

2014 ◽  
Vol 8 (1) ◽  
pp. 47-50
Author(s):  
SM Apoorva ◽  
A Suchetha ◽  
DB Mundinamane ◽  
DP Bhopale ◽  
A Bharwani ◽  
...  
Keyword(s):  
Bacterial Species ◽  
Periodontal Pocket ◽  
Human Beings ◽  
Beneficial Bacteria ◽  
Initial Attachment ◽  
Bacterial Interactions ◽  
Tooth Surfaces ◽  
Free People ◽  
Insight Into

ABSTRACT Microflora can be found in both caries-free and periodontitis-free people and caries-affected and periodontitis-affected people, and many clinical studies reveal that the portion of certain bacterial species such as Streptococcus mutans or Porphyromonas gingivalis, respectively, is increased in patients with caries or periodontitis. Therefore, it seems that the competition that results between beneficial bacteria and virulent bacteria leads to either a healthy or sick status of human beings. Competition between members of the dental microflora and there role in pocket recolonization is very complex and many antagonistic characteristics can be observed from competition for initial attachment on tooth surfaces or for later attachment to pioneer bacteria, competition from bacteriocins or hydrogen peroxide secreted and from facilitating the growth of some species which inhibit other species. To date only some of the details of these mechanisms are known. The present review will provide an overview on the prevalence of beneficial bacteria and the major mechanisms of oral bacterial interactions. Due to the large number of oral bacterial species, only the best characterized species are included in this review.

scholarly journals Horizontal Transfer of the Salmonella enterica Serovar Infantis Resistance and Virulence Plasmid pESI to the Gut Microbiota of Warm-Blooded Hosts

mBio ◽  
2016 ◽  
Vol 7 (5) ◽  
Author(s):  
Gili Aviv ◽  
Galia Rahav ◽  
Ohad Gal-Mor
Keyword(s):  
Multidrug Resistance ◽  
Gut Microbiota ◽  
Salmonella Enterica ◽  
Pathogenic Bacteria ◽  
Lactobacillus Reuteri ◽  
Bacterial Species ◽  
Microbial Evolution ◽  
Virulence Plasmid ◽  
Transmission Properties

ABSTRACT Salmonella enterica serovar Infantis is one of the prevalent salmonellae worldwide. Recently, we showed that the emergence of S . Infantis in Israel was facilitated by the acquisition of a unique megaplasmid (pESI) conferring multidrug resistance and increased virulence phenotypes. Here we elucidate the ecology, transmission properties, and regulation of pESI. We show that despite its large size (~280 kb), pESI does not impose a significant metabolic burden in vitro and that it has been recently fixed in the domestic S . Infantis population. pESI conjugation and the transcription of its pilus ( pil ) genes are inhibited at the ambient temperature (27°C) and by ≥1% bile but increased under temperatures of 37 to 41°C, oxidative stress, moderate osmolarity, and the microaerobic conditions characterizing the intestinal environment of warm-blooded animals. The pESI-encoded protein TraB and the oxygen homeostasis regulator Fnr were identified as transcriptional regulators of pESI conjugation. Using the mouse model, we show that following S . Infantis infection, pESI can be horizontally transferred to the gut microbiota, including to commensal Escherichia coli strains. Possible transfer, but not persistence, of pESI was also observed into Gram-positive mouse microbiota species, especially Lactobacillus reuteri . Moreover, pESI was demonstrated to further disseminate from gut microbiota to S. enterica serovar Typhimurium, in the context of gastrointestinal infection. These findings exhibit the ability of a selfish clinically relevant megaplasmid to distribute to and from the microbiota and suggest an overlooked role of the microbiota as a reservoir of mobile genetic elements and intermediator in the spread of resistance and virulence genes between commensals and pathogenic bacteria. IMPORTANCE Plasmid conjugation plays a key role in microbial evolution, enabling the acquisition of new phenotypes, including resistance and virulence. Salmonella enterica serovar Infantis is one of the ubiquitous salmonellae worldwide and a major cause of foodborne infections. Previously, we showed that the emergence of S . Infantis in Israel has involved the acquisition of a unique megaplasmid (pESI) conferring multidrug resistance and increased virulence phenotypes. Recently, the emergence of another S . Infantis strain carrying a pESI-like plasmid was identified in Italy, suggesting that the acquisition of pESI may be common to different emergent S . Infantis populations globally. Transmission of this plasmid to other strains or bacterial species is an alarming scenario. Understanding the ecology, regulation, and transmission properties of clinically relevant plasmids and the role of the microbiota in their spreading offers a new mechanism explaining the emergence of new pathogenic and resistant biotypes and may assist in the development of appropriate surveillance and prevention measures.

Bacteriophage Therapy: Issues and Controversies

2013 ◽  
Vol 7 (1) ◽  
pp. 25-28
Author(s):  
Sushmita Roy ◽  
Mohammad Abdullah Yusuf
Keyword(s):  
Pathogenic Bacteria ◽  
Phage Therapy ◽  
Bacterial Species ◽  
Bacterial Flora ◽  
Modern Medicine ◽  
Bacterial Metabolism ◽  
Bacterial Cells ◽  
Bacteriophage Therapy ◽  
Antimicrobial Drugs ◽  
Normal Bacterial Flora

Phage therapy is the application of bacteria-specific viruses to combat uncontrolled and undesired bacteria. The emergence of bacterial resistant to most of the currently available antimicrobial drugs has become a critical problem in modern medicine. Bacteriophages are viruses that invade bacterial cells and, in the case of lytic phages, disrupt bacterial metabolism and cause the bacteria to lyse. Owing to their host specificity which can range from an ability to infect only a few strains of a bacterial species to, more rarely, a capacity to infect more than one relatively closely related bacterial genus phages only minimally impact health-protecting normal bacterial flora. By contrast, many antibiotics, which tend to have broader spectrums of activity, are prone to inducing super infections. Phages against many pathogenic bacteria are easily discovered. In this review bacteriophages has been highlighted regarding different issues as well as controversies.DOI: http://dx.doi.org/10.3329/bjmm.v7i1.19319 Bangladesh J Med Microbiol 2013; 07(01): 25-28

scholarly journals Oligofructose and experimental model of neonatal necrotising enterocolitis

2002 ◽  
Vol 87 (S2) ◽  
pp. S213-S219 ◽  
Author(s):  
M.-J. Butel ◽  
A.-J. Waligora-Dupriet ◽  
O. Szylit
Keyword(s):  
Experimental Model ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Protective Role ◽  
Necrotising Enterocolitis ◽  
Preterm Neonates ◽  
Intestinal Lesions ◽  
Fermenting Bacteria ◽  
Neonatal Necrotising Enterocolitis

The gut of preterm neonates is colonised with a paucity of bacterial species originating more from the environment than from the mother. Furthermore, a delayed colonisation by bifidobacteria promotes colonisation by potentially pathogenic bacteria. This may contribute towards the development of neonatal necrotising enterocolitis (NEC). The physiopathology of NEC is still unclear but immaturity of the gut, enteral feeding and bacterial colonisation are all thought to be involved. None of the current preventive treatments are considered satisfactory. Modulating the autochthonous microflora by probiotics or prebiotics could be a more reliable approach to prevention. Using gnotobiotic quails as an experimental model of NEC we have shown that onset of intestinal lesions requires a combination of low endogenous lactase activity, lactose in diet, and colonisation by lactose-fermenting bacteria such as the clostridia. The protective role of bifidobacteria was demonstrated in this model through a decrease in clostridial populations and in butyric acid. Oligofructose dietary supplementation was shown to enhance this effect with an increase in the bifidobacterial level and consequently a greater decrease in clostridia. However, oligofructose was unable to promote a bifidobacterial acquisition when the microflora was initially deprived of this group. Nevertheless, oligofructose can act as an anti-infective agent and decrease the occurrence or severity of the lesions depending on the bacteria involved. According to these results and to the fact that oligosaccharides are a major component of breast milk, the addition of oligofructose in formula milks may be a nutritional approach to favouring colonisation by a beneficial flora.

scholarly journals Molecular Evidence of a Broad Range of Pathogenic Bacteria in Ctenocephalides spp.: Should We Re-Examine the Role of Fleas in the Transmission of Pathogens?

2021 ◽  
Vol 6 (1) ◽  
pp. 37
Author(s):  
Georgios Dougas ◽  
Athanassios Tsakris ◽  
Stavroula Beleri ◽  
Eleni Patsoula ◽  
Maria Linou ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Potential Role ◽  
Bacterial Species ◽  
Molecular Evidence ◽  
Dna Evidence ◽  
Streptococcus Species ◽  
Classification Of Diseases ◽  
International Statistical Classification

The internal microbiome of common cat and dog fleas was studied for DNA evidence of pathogenic bacteria. Fleas were grouped in pools by parasitized animal. DNA was extracted and investigated with 16S metagenomics for medically relevant (MR) bacteria, based on the definitions of the International Statistical Classification of Diseases and Related Health Problems (WHO). The MR bacterial species totaled 40, were found in 60% of flea-pools (N = 100), and included Acinetobacterbaumannii, Bacteroidesfragilis, Clostridiumperfringens, Enterococcusfaecalis, E. mundtii, Fusobacteriumnucleatum, Haemophilusaegyptius, Kingellakingae, Klebsiellapneumoniae, Leptotrichiabuccalis, L. hofstadii, Moraxellalacunata, Pasteurellamultocida, Propionibacteriumacnes, P. propionicum, Proteusmirabilis, Pseudomonasaeruginosa, Rickettsiaaustralis, R. hoogstraalii, Salmonellaenterica, and various Bartonella, Staphylococcus, and Streptococcus species. B. henselae (p = 0.004) and B. clarridgeiae (p = 0.006) occurred more frequently in fleas from cats, whereas Rickettsiahoogstraalii (p = 0.031) and Propionibacteriumacnes (p = 0.029) had a preference in fleas from stray animals. Most of the discovered MR species can form biofilm, and human exposure may theoretically occur through the flea-host interface. The fitness of these pathogenic bacteria to cause infection and the potential role of fleas in the transmission of a broad range of diseases should be further investigated.

The relationship between the phageome and human health: are bacteriophages beneficial or harmful microbes?

2021 ◽  
pp. 1-14
Author(s):  
L. Fernández ◽  
A.C. Duarte ◽  
A. Rodríguez ◽  
P. García
Keyword(s):  
Antibiotic Resistance ◽  
Human Health ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Phage Therapy ◽  
Negative Impact ◽  
Antibiotic Resistance Genes ◽  
Resistant Bacteria ◽  
Potential Risks

In the context of the global antibiotic resistance crisis, bacteriophages are increasingly becoming promising antimicrobial agents against multi-resistant bacteria. Indeed, a huge effort is being made to bring phage-derived products to the market, a process that will also require revising the current regulations in order to facilitate their approval. However, despite the evidence supporting the safety of phages for humans, the general public would still be reluctant to use ‘viruses’ for therapeutic purposes. In this scenario, we consider that it is important to discuss the role of these microorganisms in the equilibrium of the microbiota and how this relates to human health. To do that, this review starts by examining the role of phages as key players in bacterial communities (including those that naturally inhabit the human body), modulating the species composition and contributing to maintain a ‘healthy’ status quo. Additionally, in specific situations, e.g. an infectious disease, bacteriophages can be used as target-specific antimicrobials against pathogenic bacteria (phage therapy), while being harmless to the desirable microbiota. Apart from that, incipient research shows the potential application of these viruses to treat diseases caused by bacterial dysbiosis. This latter application would be comparable to the use of probiotics or prebiotics, since bacteriophages can indirectly improve the growth of beneficial bacteria in the gastrointestinal tract by removing undesirable competitors. On the other hand, possible adverse effects do not appear to be an impediment to promote phage therapy. Nonetheless, it is important to remember their potentially negative impact, mainly concerning their immunogenicity or their potential spread of virulence and antibiotic resistance genes, especially by temperate phages. Overall, we believe that phages should be largely considered beneficial microbes, although it is paramount not to overlook their potential risks.

scholarly journals Phage Cocktail Development against Aeromonas salmonicida subsp. salmonicida Strains Is Compromised by a Prophage

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2241
Author(s):  
Nava Hosseini ◽  
Valérie E. Paquet ◽  
Mahdi Chehreghani ◽  
Sylvain Moineau ◽  
Steve J. Charette
Keyword(s):  
Antibiotic Resistance ◽  
Food Production ◽  
Pathogenic Bacteria ◽  
Phage Therapy ◽  
Aeromonas Salmonicida ◽  
Multiplicity Of Infection ◽  
Production Sector ◽  
Phage Cocktail ◽  
Effective Use ◽  
The Impact

Aquaculture is a rapidly growing food production sector. Fish farmers are experiencing increasing problems with antibiotic resistance when fighting against pathogenic bacteria such as Aeromonas salmonicida subsp. salmonicida, the causative agent of furunculosis. Phage therapy may provide an alternative, but effective use must be determined. Here, we studied the inhibition of A. salmonicida subsp. salmonicida strains by five phages (HER98 [44RR2.8t.2], HER110 [65.2], SW69-9, L9-6 and Riv-10) used individually or as combinations of two to five phages. A particular combination of four phages (HER98 [44RR2.8t.2], SW69-9, Riv-10, and HER110 [65.2]) was found to be the most effective when used at an initial multiplicity of infection (MOI) of 1 against the A. salmonicida subsp. salmonicida strain 01-B526. The same phage cocktail is effective against other strains except those bearing a prophage (named Prophage 3), which is present in 2/3 of the strains from the province of Quebec. To confirm the impact of this prophage, we tested the effectiveness of the same cocktail on strains that were either cured or lysogenized with Prophage 3. While the parental strains were sensitive to the phage cocktail, the lysogenized ones were much less sensitive. These data indicate that the prophage content of A. salmonicida subsp. salmonicida can affect the efficacy of a cocktail of virulent phages for phage therapy purposes.

scholarly journals Analysis of Selection Methods to Develop Novel Phage Therapy Cocktails Against Antimicrobial Resistant Clinical Isolates of Bacteria

2021 ◽  
Vol 12 ◽  
Author(s):  
Melissa E. K. Haines ◽  
Francesca E. Hodges ◽  
Janet Y. Nale ◽  
Jennifer Mahony ◽  
Douwe van Sinderen ◽  
...  
Keyword(s):  
Phage Therapy ◽  
Bacterial Species ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Novel Approach ◽  
Phage Cocktail ◽  
Good Proxy ◽  
No Gold Standard ◽  
Efficient Screening ◽  
Screening Cascade

Antimicrobial resistance (AMR) is a major problem globally. The main bacterial organisms associated with urinary tract infection (UTI) associated sepsis are E. coli and Klebsiella along with Enterobacter species. These all have AMR strains known as ESBL (Extended Spectrum Beta-Lactamase), which are featured on the WHO priority pathogens list as “critical” for research. Bacteriophages (phages), as viruses that can infect and kill bacteria, could provide an effective tool to tackle these AMR strains. There is currently no “gold standard” for developing a phage cocktail. Here we describe a novel approach to develop an effective phage cocktail against a set of ESBL-producing E. coli and Klebsiella largely isolated from patients in United Kingdom hospitals. By comparing different measures of phage efficacy, we show which are the most robust, and suggest an efficient screening cascade that could be used to develop phage cocktails to target other AMR bacterial species. A target panel of 38 ESBL-producing clinical strains isolated from urine samples was collated and used to test phage efficacy. After an initial screening of 68 phages, six were identified and tested against these 38 strains to determine their clinical coverage and killing efficiency. To achieve this, we assessed four different methods to assess phage virulence across these bacterial isolates. These were the Direct Spot Test (DST), the Efficiency of Plating (EOP) assay, the planktonic killing assay (PKA) and the biofilm assay. The final ESBL cocktail of six phages could effectively kill 23/38 strains (61%), for Klebsiella 13/19 (68%) and for E. coli 10/19 (53%) based on the PKA data. The ESBL E. coli collection had six isolates from the prevalent UTI-associated ST131 sequence type, five of which were targeted effectively by the final cocktail. Of the four methods used to assess phage virulence, the data suggests that PKAs are as effective as the much more time-consuming EOPs and data for the two assays correlates well. This suggests that planktonic killing is a good proxy to determine which phages should be used in a cocktail. This assay when combined with the virulence index also allows “phage synergy” to inform cocktail design.

scholarly journals The Response Regulator PhoP Is Important for Survival under Conditions of Macrophage-Induced Stress and Virulence in Yersinia pestis

2000 ◽  
Vol 68 (6) ◽  
pp. 3419-3425 ◽  
Author(s):  
Petra C. F. Oyston ◽  
Nick Dorrell ◽  
Kerstin Williams ◽  
Shu-Rui Li ◽  
Michael Green ◽  
...  
Keyword(s):  
Gene Expression ◽  
Yersinia Pestis ◽  
Pathogenic Bacteria ◽  
Yersinia Pseudotuberculosis ◽  
Bacterial Species ◽  
Lethal Dose ◽  
Wild Type ◽  
Virulence Gene Expression

ABSTRACT The two-component regulatory system PhoPQ has been identified in many bacterial species. However, the role of PhoPQ in regulating virulence gene expression in pathogenic bacteria has been characterized only in Salmonella species. We have identified, cloned, and sequenced PhoP orthologues from Yersinia pestis,Yersinia pseudotuberculosis, and Yersinia enterocolitica. To investigate the role of PhoP in the pathogenicity of Y. pestis, an isogenic phoPmutant was constructed by using a reverse-genetics PCR-based strategy. The protein profiles of the wild-type and phoP mutant strains, grown at either 28 or 37°C, revealed more than 20 differences, indicating that PhoP has pleiotrophic effects on gene expression in Y. pestis. The mutant showed a reduced ability to survive in J774 macrophage cell cultures and under conditions of low pH and oxidative stress in vitro. The mean lethal dose of the phoP mutant in mice was increased 75-fold in comparison with that of the wild-type strain, indicating that the PhoPQ system plays a key role in regulating the virulence of Y. pestis.

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