scholarly journals Microbial Arsenal of Antiviral Defenses. Part II

2021 ◽  
Vol 86 (4) ◽  
pp. 449-470
Author(s):  
Artem B. Isaev ◽  
Olga S. Musharova ◽  
Konstantin V. Severinov
Keyword(s):  
Small Molecules ◽  
Phage Therapy ◽  
Phage Infection ◽  
Dna Modification ◽  
Bacterial Cells ◽  
Host Defenses ◽  
Abortive Infection ◽  
Microbial Genomes ◽  
Infection Mechanisms ◽  
Phage Propagation

Abstract Bacteriophages or phages are viruses that infect bacterial cells (for the scope of this review we will also consider viruses that infect Archaea). The constant threat of phage infection is a major force that shapes evolution of microbial genomes. To withstand infection, bacteria had evolved numerous strategies to avoid recognition by phages or to directly interfere with phage propagation inside the cell. Classical molecular biology and genetic engineering had been deeply intertwined with the study of phages and host defenses. Nowadays, owing to the rise of phage therapy, broad application of CRISPR-Cas technologies, and development of bioinformatics approaches that facilitate discovery of new systems, phage biology experiences a revival. This review describes variety of strategies employed by microbes to counter phage infection. In the first part defense associated with cell surface, roles of small molecules, and innate immunity systems relying on DNA modification were discussed. The second part focuses on adaptive immunity systems, abortive infection mechanisms, defenses associated with mobile genetic elements, and novel systems discovered in recent years through metagenomic mining.

scholarly journals Microbial Arsenal of Antiviral Defenses – Part I

2021 ◽  
Vol 86 (3) ◽  
pp. 319-337
Author(s):  
Artem B. Isaev ◽  
Olga S. Musharova ◽  
Konstantin V. Severinov
Keyword(s):  
Small Molecules ◽  
Phage Therapy ◽  
Phage Infection ◽  
Dna Modification ◽  
Bacterial Cells ◽  
Host Defenses ◽  
Microbial Genomes ◽  
Broad Application ◽  
Phage Propagation

Abstract Bacteriophages or phages are viruses that infect bacterial cells (for the scope of this review we will also consider viruses that infect Archaea). Constant threat of phage infection is a major force that shapes evolution of the microbial genomes. To withstand infection, bacteria had evolved numerous strategies to avoid recognition by phages or to directly interfere with phage propagation inside the cell. Classical molecular biology and genetic engineering have been deeply intertwined with the study of phages and host defenses. Nowadays, owing to the rise of phage therapy, broad application of CRISPR-Cas technologies, and development of bioinformatics approaches that facilitate discovery of new systems, phage biology experiences a revival. This review describes variety of strategies employed by microbes to counter phage infection, with a focus on novel systems discovered in recent years. First chapter covers defense associated with cell surface, role of small molecules, and innate immunity systems relying on DNA modification.

scholarly journals Phage infection and sub-lethal antibiotic exposure mediate Enterococcus faecalis type VII secretion system dependent inhibition of bystander bacteria

2020 ◽  
Author(s):  
Anushila Chatterjee ◽  
Julia L. E. Willett ◽  
Gary M. Dunny ◽  
Breck A. Duerkop
Keyword(s):  
Bacterial Infections ◽  
Phage Therapy ◽  
Secretion System ◽  
Phage Infection ◽  
Collateral Damage ◽  
Bacterial Cells ◽  
Antibiotic Exposure ◽  
Type Vii Secretion ◽  
Type Vii Secretion System ◽  
Polymicrobial Communities

AbstractBacteriophages (phages) are being considered as alternative therapeutics for the treatment of multidrug resistant bacterial infections. Considering phages have narrow host-ranges, it is generally accepted that therapeutic phages will have a marginal impact on non-target bacteria. We have discovered that lytic phage infection induces transcription of type VIIb secretion system (T7SS) genes in the pathobiont Enterococcus faecalis. Membrane damage during phage infection induces T7SS gene expression resulting in cell contact dependent antagonism of different Gram positive bystander bacteria. Deletion of essB, a T7SS structural component, abrogates phage-mediated killing of bystanders. A predicted immunity gene confers protection against T7SS mediated inhibition, and disruption of its upstream LXG toxin gene rescues growth of E. faecalis and Staphylococcus aureus bystanders. Phage induction of T7SS gene expression and bystander inhibition requires IreK, a serine/threonine kinase, and OG1RF_11099, a predicted GntR-family transcription factor. Additionally, sub-lethal doses of membrane targeting and DNA damaging antibiotics activated T7SS expression independent of phage infection, triggering T7SS antibacterial activity against bystander bacteria. Our findings highlight how phage infection and antibiotic exposure of a target bacterium can affect non-target bystander bacteria and implies that therapies beyond antibiotics, such as phage therapy, could impose collateral damage to polymicrobial communities.Author SummaryRenewed interest in phages as alternative therapeutics to combat multi-drug resistant bacterial infections, highlights the importance of understanding the consequences of phage-bacteria interactions in the context of microbial communities. Although it is well established that phages are highly specific for their host bacterium, there is no clear consensus on whether or not phage infection (and thus phage therapy) would impose collateral damage to non-target bacteria in polymicrobial communities. Here we provide direct evidence of how phage infection of a clinically relevant pathogen triggers an intrinsic type VII secretion system (T7SS) antibacterial response that consequently restricts the growth of neighboring bacterial cells that are not susceptible to phage infection. Phage induction of T7SS activity is a stress response and in addition to phages, T7SS antagonism can be induced using sub-inhibitory concentrations of antibiotics that facilitate membrane or DNA damage. Together these data show that a bacterial pathogen responds to diverse stressors to induce T7SS activity which manifests through the antagonism of neighboring non-kin bystander bacterial cells.

scholarly journals Cell wall deficiency as an escape mechanism from phage infection

Open Biology ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 210199
Author(s):  
Véronique Ongenae ◽  
Ariane Briegel ◽  
Dennis Claessen
Keyword(s):  
Cell Wall ◽  
Phage Therapy ◽  
Cell Envelope ◽  
Environmental Stresses ◽  
Phage Infection ◽  
Abortive Infection ◽  
Escape Mechanism ◽  
A Cell ◽  
Restriction Modification ◽  
Unwanted Consequence

The cell wall plays a central role in protecting bacteria from some environmental stresses, but not against all. In fact, in some cases, an elaborate cell envelope may even render the cell more vulnerable. For example, it contains molecules or complexes that bacteriophages recognize as the first step of host invasion, such as proteins and sugars, or cell appendages such as pili or flagella. In order to counteract phages, bacteria have evolved multiple escape mechanisms, such as restriction-modification, abortive infection, CRISPR/Cas systems or phage inhibitors. In this perspective review, we present the hypothesis that bacteria may have additional means to escape phage attack. Some bacteria are known to be able to shed their cell wall in response to environmental stresses, yielding cells that transiently lack a cell wall. In this wall-less state, the bacteria may be temporarily protected against phages, since they lack the essential entities that are necessary for phage binding and infection. Given that cell wall deficiency can be triggered by clinically administered antibiotics, phage escape could be an unwanted consequence that limits the use of phage therapy for treating stubborn infections.

scholarly journals Aminoglycoside Antibiotics Inhibit Mycobacteriophage Infection

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 714 ◽  
Author(s):  
Zheng Jiang ◽  
Junwei Wei ◽  
Yunxiang Liang ◽  
Nan Peng ◽  
Yingjun Li
Keyword(s):  
Antibiotic Resistance ◽  
Mycobacterium Tuberculosis ◽  
Structural Analysis ◽  
Global Health ◽  
Broad Spectrum ◽  
Phage Therapy ◽  
Amino Sugar ◽  
Aminoglycoside Antibiotics ◽  
Phage Infection ◽  
Drug Resistant

Antibiotic resistance is becoming the biggest threat to global health. At the same time, phage therapy is witnessing a return of interest. The therapeutic use of bacteriophages that infect and kill bacteria is a suitable strategy to combat antibiotic resistance. Furthermore, bacteriophages are increasingly used in combination with standard antibiotics against drug-resistant pathogens. Interestingly, we found that the engineered mycobacteriophage phAE159 and natural phage D29 cannot infect the Mycobacterium tuberculosis in the presence of kanamycin, hygromycin or streptomycin, but the phage infection was not affected in the presence of spectinomycin. Based on a series of studies and structural analysis of the above four aminoglycoside antibiotics, it could be speculated that the amino sugar group of aminoglycoside might selectively inhibit mycobacteriophage DNA replication. Our discovery that broad-spectrum antibiotics inhibit phage infection is of great value. This study will provide guidance for people to combine phage and antibiotics to treat M. tuberculosis.

scholarly journals BaeSR, Involved in Envelope Stress Response, Protects against Lysogenic Conversion by Shiga Toxin 2-Encoding Phages

2015 ◽  
Vol 83 (4) ◽  
pp. 1451-1457 ◽  
Author(s):  
Lejla Imamovic ◽  
Alexandre Martínez-Castillo ◽  
Carmen Benavides ◽  
Maite Muniesa
Keyword(s):  
Stress Responses ◽  
Shiga Toxin ◽  
Phage Infection ◽  
Bacterial Cells ◽  
Content Type ◽  
Signaling Systems ◽  
E Coli ◽  
Envelope Stress ◽  
Lysogenic Conversion

Infection and lysogenic conversion with Shiga toxin-encoding bacteriophages (Stx phages) drive the emergence of new Shiga toxin-producingEscherichia colistrains. Phage attachment to the bacterial surface is the first stage of phage infection. Envelope perturbation causes activation of envelope stress responses in bacterial cells. Although many external factors are known to activate envelope stress responses, the role of these responses in the phage-bacterium interaction remains unexplored. Here, we investigate the link between three envelope signaling systems inE. coli(RcsBC, CpxAR, and BaeSR) and Stx2 phage infection by determining the success of bacterial lysogenic conversion. For this purpose,E. coliDH5α wild-type (WT) and mutant strains lacking RcsBC, CpxAR, or BaeSR signaling systems were incubated with a recombinant Stx2 phage (933W). Notably, the number of lysogens obtained with the BaeSR mutant was 5 log10units higher than with the WT, and the same differences were observed when using 7 different Stx2 phages. To assess whether the membrane receptor used by Stx phages, BamA, was involved in the differences observed,bamAgene expression was monitored by reverse transcription-quantitative PCR (RT-qPCR) in all host strains. A 4-fold-higherbamAexpression level was observed in the BaeSR mutant than in the WT strain, suggesting that differential expression of the receptor used by Stx phages accounted for the increase in the number of lysogenization events. Establishing the link between the role of stress responses and phage infection has important implications for understanding the factors affecting lysogenic conversion, which drives the emergence of new pathogenic clones.

scholarly journals AbiA, a Lactococcal Abortive Infection Mechanism Functioning in Streptococcus thermophilus

2002 ◽  
Vol 68 (12) ◽  
pp. 6388-6391 ◽  
Author(s):  
Mark Tangney ◽  
Gerald F. Fitzgerald
Keyword(s):  
Growth Temperature ◽  
Streptococcus Thermophilus ◽  
Abortive Infection ◽  
Infection Mechanism ◽  
Infection Mechanisms

ABSTRACT The lactococcal abortive infection mechanisms AbiA and AbiG were introduced into Streptococcus thermophilus 4035, and a range of phages capable of infecting this host were examined for sensitivity to these mechanisms. AbiA proved effective against six phages when examined at a growth temperature of 30°C but had no effect on any of the phages when tested at 37 or 42°C. AbiG failed to affect any of the S. thermophilus phages at 30, 37, or 42°C.

scholarly journals Phage–Bacteria Interactions in Potential Applications of Bacteriophage vB_EfaS-271 against Enterococcus faecalis

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 318
Author(s):  
Gracja Topka-Bielecka ◽  
Bożena Nejman-Faleńczyk ◽  
Sylwia Bloch ◽  
Aleksandra Dydecka ◽  
Agnieszka Necel ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Mammalian Cells ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Bacterial Species ◽  
Resistant Bacteria ◽  
Bacterial Cells ◽  
Potential Applications ◽  
High Level

Phage therapy is one of main alternative option for antibiotic treatment of bacterial infections, particularly in the era of appearance of pathogenic strains revealing resistance to most or even all known antibiotics. Enterococcus faecalis is one of such pathogens causing serious human infections. In the light of high level of biodiversity of bacteriophages and specificity of phages to bacterial species or even strains, development of effective phage therapy depend, between others, on identification and characterization of a large collection of these viruses, including understanding of their interactions with host bacterial cells. Recently, isolation of molecular characterization of bacteriophage vB_EfaS-271, infecting E. faecalis strains have been reported. In this report, phage–host interactions are reported, including ability of vB_EfaS-271 to infect bacteria forming biofilms, efficiency of eliminating bacterial cells from cultures depending on multiplicity of infection (m.o.i.), toxicity of purified phage particles to mammalian cells, and efficiency of appearance of phage-resistant bacteria. The presented results indicate that vB_EfaS-271 can significantly decrease number of viable E. faecalis cells in biofilms and in liquid cultures and reveals no considerable toxicity to mammalian cells. Efficiency of formation of phage-resistant bacteria was dependent on m.o.i. and was higher when the virion-cell ratio was as high as 10 than at low (between 0.01 and 0.0001) m.o.i. values. We conclude that vB_EfaS-271 may be considered as a candidate for its further use in phage therapy.

scholarly journals Phage Therapy, The Best Choice To Overcome Antibiotic Resistance, But Can Never Replace Antibiotics

2020 ◽  
Vol 4 (12) ◽  
pp. 01-05
Author(s):  
G. Sunil paul
Keyword(s):  
Antibiotic Resistance ◽  
Life Cycle ◽  
Antimicrobial Therapy ◽  
Phage Therapy ◽  
Acquired Resistance ◽  
Effective Alternative ◽  
Clinical Use ◽  
Bacterial Cells ◽  
Western Countries ◽  
Life Threatening

within the bacteria. Phage therapy is the clinical use of these bacteriophages to treat infections caused by superbugs (bacteria that have acquired resistance against antibiotics). Phages when administered in to bacteria, causes the lysis of the bacterial cells in the lytic phase of phage life cycle. Phage therapy has acquired its importance in the recent years after their successful use in managing some life threatening infections and helped in saving lives. Phage therapy is currently being used as the antimicrobial therapy in some western countries. this paper mainly discusses about using phage therapy in treating infections caused by superbugs, and also discusses on what measures should be taken by different countries to successfully introduce the phage therapy in clinical use. Apart from this phage therapy has got some disadvantages which shows that phage therapy can never be an effective alternative for antibiotics. We conclude that phage therapy can be the best choice for treating infections caused by superbugs, where antibiotics can’t work but can’t be used again once used before in a particular patient.

scholarly journals Parallel Genomics Uncover Novel Enterococcal-Bacteriophage Interactions

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Anushila Chatterjee ◽  
Julia L. E. Willett ◽  
Uyen Thy Nguyen ◽  
Brendan Monogue ◽  
Kelli L. Palmer ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Response Regulator ◽  
Burst Size ◽  
Bacterial Community Composition ◽  
Model Organism ◽  
Phage Infection ◽  
Bacterial Cells ◽  
Transcriptomic Profiling ◽  
Bacterial Gene ◽  
Content Type

ABSTRACT Bacteriophages (phages) have been proposed as alternative therapeutics for the treatment of multidrug-resistant bacterial infections. However, there are major gaps in our understanding of the molecular events in bacterial cells that control how bacteria respond to phage predation. Using the model organism Enterococcus faecalis, we used two distinct genomic approaches, namely, transposon library screening and RNA sequencing, to investigate the interaction of E. faecalis with a virulent phage. We discovered that a transcription factor encoding a LytR family response regulator controls the expression of enterococcal polysaccharide antigen (epa) genes that are involved in phage infection and bacterial fitness. In addition, we discovered that DNA mismatch repair mutants rapidly evolve phage adsorption deficiencies, underpinning a molecular basis for epa mutation during phage infection. Transcriptomic profiling of phage-infected E. faecalis revealed broad transcriptional changes influencing viral replication and progeny burst size. We also demonstrate that phage infection alters the expression of bacterial genes associated with intra- and interbacterial interactions, including genes involved in quorum sensing and polymicrobial competition. Together, our results suggest that phage predation has the potential to influence complex microbial behavior and may dictate how bacteria respond to external environmental stimuli. These responses could have collateral effects (positive or negative) on microbial communities, such as the host microbiota, during phage therapy. IMPORTANCE We lack fundamental understanding of how phage infection influences bacterial gene expression and, consequently, how bacterial responses to phage infection affect the assembly of polymicrobial communities. Using parallel genomic approaches, we have discovered novel transcriptional regulators and metabolic genes that influence phage infection. The integration of whole-genome transcriptomic profiling during phage infection has revealed the differential regulation of genes important for group behaviors and polymicrobial interactions. Our work suggests that therapeutic phages could more broadly influence bacterial community composition outside their intended host targets.

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