The Age of Phage: Friend or Foe in the New Dawn of Therapeutic and Biocontrol Applications?

Extended overuse and misuse of antibiotics and other antibacterial agents has resulted in an antimicrobial resistance crisis. Bacteriophages, viruses that infect bacteria, have emerged as a legitimate alternative antibacterial agent with a wide scope of applications which continue to be discovered and refined. However, the potential of some bacteriophages to aid in the acquisition, maintenance, and dissemination of negatively associated bacterial genes, including resistance and virulence genes, through transduction is of concern and requires deeper understanding in order to be properly addressed. In particular, their ability to interact with mobile genetic elements such as plasmids, genomic islands, and integrative conjugative elements (ICEs) enables bacteriophages to contribute greatly to bacterial evolution. Nonetheless, bacteriophages have the potential to be used as therapeutic and biocontrol agents within medical, agricultural, and food processing settings, against bacteria in both planktonic and biofilm environments. Additionally, bacteriophages have been deployed in developing rapid, sensitive, and specific biosensors for various bacterial targets. Intriguingly, their bioengineering capabilities show great promise in improving their adaptability and effectiveness as biocontrol and detection tools. This review aims to provide a balanced perspective on bacteriophages by outlining advantages, challenges, and future steps needed in order to boost their therapeutic and biocontrol potential, while also providing insight on their potential role in contributing to bacterial evolution and survival.

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A MyD88-Deficient Mouse Model Reveals a Role for Nramp1 in Campylobacter jejuni Infection

Infection and Immunity ◽

10.1128/iai.01216-06 ◽

2007 ◽

Vol 75 (4) ◽

pp. 1994-2003 ◽

Cited By ~ 50

Author(s):

Robert O. Watson ◽

Veronica Novik ◽

Dirk Hofreuter ◽

María Lara-Tejero ◽

Jorge E. Galán

Keyword(s):

Campylobacter Jejuni ◽

Virulence Genes ◽

Potential Role ◽

Bacterial Pathogen ◽

Adaptor Protein ◽

Myeloid Differentiation ◽

Deficient Mouse ◽

Immunocompetent Mice ◽

Myeloid Differentiation Factor ◽

Deficient Mice

ABSTRACT Campylobacter jejuni is a major worldwide cause of enteric illnesses. Adult immunocompetent mice are not susceptible to C. jejuni infection. However, we show here that mice deficient in the adaptor protein myeloid differentiation factor 88 (MyD88), which is required for signaling through most Toll-like receptors, can be stably colonized by C. jejuni but not by isogenic derivatives carrying mutations in known virulence genes. We also found that Nramp1 deficiency increases the mouse susceptibility to C. jejuni infection when administered systemically. These results indicate that MyD88-deficient mice could be a useful model to study C. jejuni colonization and reveal a potential role for Nramp1 in the control of this bacterial pathogen.

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Molecular insights into the genome dynamics and interactions between core and acquired genomes ofVibrio cholerae

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2006283117 ◽

2020 ◽

Vol 117 (38) ◽

pp. 23762-23773

Author(s):

Archana Pant ◽

Satyabrata Bag ◽

Bipasa Saha ◽

Jyoti Verma ◽

Pawan Kumar ◽

...

Keyword(s):

Bacterial Species ◽

Bacterial Genome ◽

Genomic Islands ◽

Host Bacterium ◽

Metabolic Functions ◽

Bipartite Genome ◽

Ctx Prophage ◽

Integrative Conjugative Elements

Bacterial species are hosts to horizontally acquired mobile genetic elements (MGEs), which encode virulence, toxin, antimicrobial resistance, and other metabolic functions. The bipartite genome ofVibrio choleraeharbors sporadic and conserved MGEs that contribute in the disease development and survival of the pathogens. For a comprehensive understanding of dynamics of MGEs in the bacterial genome, we engineered the genome ofV. choleraeand examined in vitro and in vivo stability of genomic islands (GIs), integrative conjugative elements (ICEs), and prophages. Recombinant vectors carrying the integration module of these GIs, ICE and CTXΦ, helped us to understand the efficiency of integrations of MGEs in theV. choleraechromosome. We have deleted more than 250 acquired genes from 6 different loci in theV. choleraechromosome and showed contribution of CTX prophage in the essentiality of SOS response master regulator LexA, which is otherwise not essential for viability in other bacteria, includingEscherichia coli. In addition, we observed that the core genome-encoded RecA helps CTXΦ to bypassV. choleraeimmunity and allow it to replicate in the host bacterium in the presence of similar prophage in the chromosome. Finally, our proteomics analysis reveals the importance of MGEs in modulating the levels of cellular proteome. This study engineered the genome ofV. choleraeto remove all of the GIs, ICEs, and prophages and revealed important interactions between core and acquired genomes.

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Variability in Assembly of Degradation Operons for Naphthalene and its derivative, Carbaryl, Suggests Mobilization through Horizontal Gene Transfer

Genes ◽

10.3390/genes10080569 ◽

2019 ◽

Vol 10 (8) ◽

pp. 569 ◽

Cited By ~ 7

Author(s):

Phale ◽

Shah ◽

Malhotra

Keyword(s):

Gene Transfer ◽

Horizontal Gene Transfer ◽

Food Web ◽

Microbial Communities ◽

Metabolic Pathways ◽

Anthropogenic Activities ◽

Genetic Material ◽

Genomic Islands ◽

Biochemical Pathways ◽

Integrative Conjugative Elements

In the biosphere, the largest biological laboratory, increased anthropogenic activities have led microbes to evolve and adapt to the changes occurring in the environment. Compounds, specifically xenobiotics, released due to such activities persist in nature and undergo bio-magnification in the food web. Some of these compounds act as potent endocrine disrupters, mutagens or carcinogens, and therefore their removal from the environment is essential. Due to their persistence, microbial communities have evolved to metabolize them partially or completely. Diverse biochemical pathways have evolved or been assembled by exchange of genetic material (horizontal gene transfer) through various mobile genetic elements like conjugative and non-conjugative plasmids, transposons, phages and prophages, genomic islands and integrative conjugative elements. These elements provide an unlimited opportunity for genetic material to be exchanged across various genera, thus accelerating the evolution of a new xenobiotic degrading phenotype. In this article, we illustrate examples of the assembly of metabolic pathways involved in the degradation of naphthalene and its derivative, Carbaryl, which are speculated to have evolved or adapted through the above-mentioned processes.

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Rapid detection by multiplex PCR of Genomic Islands, prophages and Integrative Conjugative Elements in V. cholerae 7th pandemic variants

Journal of Microbiological Methods ◽

10.1016/j.mimet.2011.10.017 ◽

2012 ◽

Vol 88 (1) ◽

pp. 98-102 ◽

Cited By ~ 8

Author(s):

Matteo Spagnoletti ◽

Daniela Ceccarelli ◽

Mauro M. Colombo

Keyword(s):

Multiplex Pcr ◽

Rapid Detection ◽

Genomic Islands ◽

Integrative Conjugative Elements

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Antibiotic resistance and virulence of Escherichia coli strains isolated from animal rendering plant

Scientific Reports ◽

10.1038/s41598-020-72851-5 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Gabriela Gregova ◽

Vladimir Kmet

Keyword(s):

Escherichia Coli ◽

Antibacterial Agents ◽

Virulence Genes ◽

Gene Encoding ◽

Antibiotic Resistant ◽

Beta Lactamases ◽

E Coli ◽

Animal Wastes ◽

Extended Spectrum Beta Lactamases ◽

High Level

Abstract Processing of animal carcasses and other animal wastes in rendering plants is a significant source of antibiotic resistant microorganisms. The main goal of this study was to investigate the resistance to 18 antibacterial agents including β-lactams, fluoroquinolones, colistin and virulence factors (iss, tsh, cvaC, iutA, papC, kps and ibeA genes) in 88 Escherichia coli strains isolated from a rendering plant over 1 year period. ESBL (Extended-spectrum beta-lactamases) and plasmid-mediated Amp were screened by interpretative reading of MIC. ESBL phenotype was detected in 20.4% of samples and high level of resistance to fluoroquinolone was found in 27.2% of strains. Cephalosporinase CTX-M1, cephamycinase CMY-2, integrase 1 and transposon 3 genes were detected by PCR. Furthermore, there were found three CMY-2 producing E. coli with O25b-ST131, resistant to the high level of enrofloxacin and containing the gene encoding the ferric aerobactin receptor (iutA). One enrofloxacin resistant E. coli strain possessed iss, ibeA, kps and papC virulence genes also with CMY-2, integrase1 and Tn3. ST131 E. coli with CMY-2 has a zoonotic potential and presents a serious health risk to humans.

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Genomic Analysis of a Serotype 5Streptococcus pneumoniaeOutbreak in British Columbia, Canada, 2005–2009

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2016/5381871 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Ruth R. Miller ◽

Morgan G. I. Langille ◽

Vincent Montoya ◽

Anamaria Crisan ◽

Aleksandra Stefanovic ◽

...

Keyword(s):

British Columbia ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Genomic Island ◽

Wide Spectrum ◽

Health Agency ◽

Genomic Islands ◽

Great Promise ◽

Whole Genome ◽

Serotype 5

Background.Streptococcus pneumoniaecan cause a wide spectrum of disease, including invasive pneumococcal disease (IPD). From 2005 to 2009 an outbreak of IPD occurred in Western Canada, caused by aS. pneumoniaestrain with multilocus sequence type (MLST) 289 and serotype 5. We sought to investigate the incidence of IPD due to thisS. pneumoniaestrain and to characterize the outbreak in British Columbia using whole-genome sequencing.Methods. IPD was defined according to Public Health Agency of Canada guidelines. Two isolates representing the beginning and end of the outbreak were whole-genome sequenced. The sequences were analyzed for single nucleotide variants (SNVs) and putative genomic islands.Results. The peak of the outbreak in British Columbia was in 2006, when 57% of invasiveS. pneumoniaeisolates were serotype 5. Comparison of two whole-genome sequenced strains showed only 10 SNVs between them. A 15.5 kb genomic island was identified in outbreak strains, allowing the design of a PCR assay to track the spread of the outbreak strain.Discussion. We show that the serotype 5 MLST 289 strain contains a distinguishing genomic island, which remained genetically consistent over time. Whole-genome sequencing holds great promise for real-time characterization of outbreaks in the future and may allow responses tailored to characteristics identified in the genome.

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A Comprehensive Assessment of the Safety of Blautia producta DSM 2950

Microorganisms ◽

10.3390/microorganisms9050908 ◽

2021 ◽

Vol 9 (5) ◽

pp. 908

Author(s):

Xuemei Liu ◽

Weiling Guo ◽

Shumao Cui ◽

Xin Tang ◽

Jianxin Zhao ◽

...

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Virulence Genes ◽

Antibiotic Resistance Genes ◽

Pharmaceutical Preparations ◽

Genomic Islands ◽

Poly I:C ◽

Toxicity Tests ◽

Oral Toxicity ◽

Acute Toxicity Tests

In recent years, Blautia has attracted attention for its role in ameliorating host diseases. In particular, Blautia producta DSM 2950 has been considered a potential probiotic due to its ability to mitigate inflammation in poly(I:C) induced HT-29 cells. Thus, to promote the development of indigenous intestinal microorganisms with potential probiotic function, we conducted a comprehensive experimental analysis of DSM 2950 to determine its safety. This comprised a study of its potential virulence genes, antibiotic resistance genes, genomic islands, antibiotic resistance, and hemolytic activity and a 14-day test of its acute oral toxicity in mice. The results indicated no toxin-related virulence genes in the DSM 2950 genome. Most of the genomic islands in DSM 2950 were related to metabolism, rather than virulence expression. DSM 2950 was sensitive to most of the tested antibiotics but was tolerant of treatment with kanamycin, neomycin, clindamycin, or ciprofloxacin, probably because it possessed the corresponding antibiotic resistance genes. Oral acute toxicity tests indicated that the consumption of DSM 2950 does not cause toxic side effects in mice. Overall, the safety profile of DSM 2950 confirmed that it could be a candidate probiotic for use in food and pharmaceutical preparations.

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