scholarly journals Genome-driven elucidation of phage-host interplay and impact of phage resistance evolution on bacterial fitness

2021 ◽  
Author(s):  
Pawel Markwitz ◽  
Cédric Lood ◽  
Tomasz Olszak ◽  
Vera van Noort ◽  
Rob Lavigne ◽  
...  
Keyword(s):  
Growth Rate ◽  
Ecological Impact ◽  
Resistance Mechanisms ◽  
Large Deletion ◽  
Carrier State ◽  
Cross Resistance ◽  
Phage Resistance ◽  
Lytic Phage ◽  
Bacterial Growth Rate ◽  
Resistance Evolution

AbstractWhen considering the interactions between bacteriophages and their host, the issue of phage-resistance emergence is a key element in understanding the ecological impact of phages on the bacterial population. It is also an essential parameter for the implementation of phage therapy to combat antibiotic-resistant pathogens. This study investigates the phenotypic and genetic responses of five Pseudomonas aeruginosa strains (PAO1, A5803, AA43, CHA, and PAK) to the infection by seven phages with distinct evolutionary backgrounds and recognised receptors (LPS/T4P). Emerging phage-insensitivity was generally accompanied by self and cross-resistance mechanisms. Significant differences were observed between the reference PAO1 responses compared to other clinical representatives. LPS-dependent phage infections in clinical strains selected for mutations in the “global regulatory” and “other” genes, rather than in the LPS-synthesis clusters detected in PAO1 clones. Reduced fitness, as proxied by the growth rate, was correlated with large deletion (20–500 kbp) and phage carrier state. Multi-phage resistance was significantly correlated with a reduced growth rate but only in the PAO1 population. In addition, we observed that the presence of prophages decreased the lytic phage maintenance seemingly protecting the host against carrier state and occasional lytic phage propagation, thus preventing a significant reduction in bacterial growth rate.

scholarly journals Interactions between the Prophage 919TP and Its Vibrio cholerae Host: Implications of gmd Mutation for Phage Resistance, Cell Auto-Aggregation, and Motility

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2342
Author(s):  
Na Li ◽  
Yigang Zeng ◽  
Bijie Hu ◽  
Tongyu Zhu ◽  
Sine Lo Svenningsen ◽  
...  
Keyword(s):  
Bacterial Pathogen ◽  
Genomic Analysis ◽  
Resistant Mutant ◽  
Resistance Mechanisms ◽  
Phage Resistance ◽  
Comparative Genomic ◽  
Lytic Phage ◽  
O Antigen ◽  
Trade Offs ◽  
Base Pair Deletion

Prophage 919TP is widely distributed among Vibrio cholera and is induced to produce free φ919TP phage particles. However, the interactions between prophage φ919TP, the induced phage particle, and its host remain unknown. In particular, phage resistance mechanisms and potential fitness trade-offs, resulting from phage resistance, are unresolved. In this study, we examined a prophage 919TP-deleted variant of V. cholerae and its interaction with a modified lytic variant of the induced prophage (φ919TP cI-). Specifically, the phage-resistant mutant was isolated by challenging a prophage-deleted variant with lytic phage φ919TP cI-. Further, the comparative genomic analysis of wild-type and φ919TP cI--resistant mutant predicted that phage φ919TP cI- selects for phage-resistant mutants harboring a mutation in key steps of lipopolysaccharide (LPS) O-antigen biosynthesis, causing a single-base-pair deletion in gene gmd. Our study showed that the gmd-mediated O-antigen defect can cause pleiotropic phenotypes, e.g., cell autoaggregation and reduced swarming motility, emphasizing the role of phage-driven diversification in V. cholerae. The developed approach assists in the identification of genetic determinants of host specificity and is used to explore the molecular mechanism underlying phage-host interactions. Our findings contribute to the understanding of prophage-facilitated horizontal gene transfer and emphasize the potential for developing new strategies to optimize the use of phages in bacterial pathogen control.

scholarly journals Correction: Population Dynamics of a Salmonella Lytic Phage and Its Host: Implications of the Host Bacterial Growth Rate in Modelling

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0136007 ◽  
Author(s):  
Sílvio B. Santos ◽  
Carla Carvalho ◽  
Joana Azeredo ◽  
Eugénio C. Ferreira
Keyword(s):  
Growth Rate ◽  
Population Dynamics ◽  
Bacterial Growth ◽  
Lytic Phage ◽  
Bacterial Growth Rate

scholarly journals Population Dynamics of a Salmonella Lytic Phage and Its Host: Implications of the Host Bacterial Growth Rate in Modelling

PLoS ONE ◽  
2014 ◽  
Vol 9 (7) ◽  
pp. e102507 ◽  
Author(s):  
Sílvio B. Santos ◽  
Carla Carvalho ◽  
Joana Azeredo ◽  
Eugénio C. Ferreira
Keyword(s):  
Growth Rate ◽  
Population Dynamics ◽  
Bacterial Growth ◽  
Lytic Phage ◽  
Bacterial Growth Rate

scholarly journals Combined Effect of the Cfr Methyltransferase and Ribosomal Protein L3 Mutations on Resistance to Ribosome-Targeting Antibiotics

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Kevin K. Pakula ◽  
Lykke H. Hansen ◽  
Birte Vester
Keyword(s):  
Growth Rate ◽  
Ribosomal Protein ◽  
Resistance Mechanisms ◽  
Antagonistic Effect ◽  
Combined Effect ◽  
23S Rrna ◽  
Cross Resistance ◽  
Content Type ◽  
Moderate Growth ◽  
Ribosomal Protein L3

ABSTRACT Several groups of antibiotics inhibit bacterial growth by binding to bacterial ribosomes. Mutations in ribosomal protein L3 have been associated with resistance to linezolid and tiamulin, which both bind at the peptidyl transferase center in the ribosome. Resistance to these and other antibiotics also occurs through methylation of 23S rRNA at position A2503 by the methyltransferase Cfr. The mutations in L3 and the cfr gene have been found together in clinical isolates, raising the question of whether they have a combined effect on antibiotic resistance or growth. We transformed a plasmid-borne cfr gene into a uL3-depleted Escherichia coli strain containing either wild-type L3 or L3 with one of seven mutations, G147R, Q148F, N149S, N149D, N149R, Q150L, or T151P, expressed from plasmid-carried rplC genes. The L3 mutations are well tolerated, with small to moderate growth rate decreases. The presence of Cfr has a very minor influence on the growth rate. The resistance of the transformants to linezolid, tiamulin, florfenicol, and Synercid (a combination of quinupristin and dalfopristin [Q-D]) was measured by MIC assays. The resistance from Cfr was, in all cases, stronger than the effects of the L3 mutations, but various effects were obtained with the combinations of Cfr and L3 mutations ranging from a synergistic to an antagonistic effect. Linezolid and tiamulin susceptibility varied greatly among the L3 mutations, while no significant effects on florfenicol and Q-D susceptibility were seen. This study underscores the complex interplay between various resistance mechanisms and cross-resistance, even from antibiotics with overlapping binding sites.

scholarly journals Phage cocktail strategies for the suppression of a pathogen in a cross-feeding coculture

2020 ◽  
Author(s):  
Lisa Fazzino ◽  
Jeremy Anisman ◽  
Jeremy M. Chacón ◽  
William R. Harcombe
Keyword(s):  
Growth Rate ◽  
Microbial Communities ◽  
Cross Resistance ◽  
Physiological Parameter ◽  
Lytic Phage ◽  
Ecological Interaction ◽  
E Coli ◽  
Phage Cocktail ◽  
Pathogen Suppression ◽  
Feeding Interactions

SummaryCocktail combinations of bacteria-infecting viruses (bacteriophage), can suppress pathogenic bacterial growth. However, predicting how phage cocktails influence microbial communities with complex ecological interactions, specifically cross-feeding interactions in which bacteria exchange nutrients, remains challenging. Here, we used experiments and mathematical simulations to determine how to best suppress a model pathogen, E. coli, when obligately cross-feeding with S. enterica. We tested whether the duration of pathogen suppression caused by a two-lytic phage cocktail was maximized when both phage targeted E. coli, or when one phage targeted E. coli and the other its cross-feeding partner, S. enterica. Experimentally, we observed that cocktails targeting both cross-feeders suppressed E. coli growth longer than cocktails targeting only E. coli. Two non-mutually-exclusive mechanisms could explain these results: 1) we found that treatment with two E. coli phage led to the evolution of a mucoid phenotype that provided cross-resistance against both phage, and 2) S. enterica set the growth rate of the co-culture, and therefore targeting S. enterica had a stronger effect on pathogen suppression. Simulations suggested that cross-resistance and the relative growth rates of cross-feeders modulated the duration of E. coli suppression. More broadly, we describe a novel bacteriophage cocktail strategy for pathogens that cross-feed.Originality-Significance StatementCross-feeding, or exchanging nutrients among bacteria, is a type of ecological interaction found in many important microbial communities. Furthermore, cross-feeding interactions are found to play a role in some infections, and research into treating infections with combinations of bacteriophage in ‘cocktails’ is growing. Here, we used a combination of mathematical modelling and wet-lab experiments to optimize suppression of a model pathogen with a bacteriophage cocktail in a synthetic cross-feeding bacterial coculture. A key finding was that a physiological parameter – growth rate – of the bacteria was important to consider when choosing the most effective cocktail formulation. This work is novel because it highlights an unexpected multispecies-targeting strategy for designing phage cocktails for cross-feeding pathogens and has relevance to many ecological systems ranging from human health to agriculture. We demonstrate how leveraging knowledge of a pathogen’s ecological interaction has the potential to improve precision medicine and management of microbial systems.

Target-Site Resistance Mechanisms to Tribenuron-methyl and Cross-resistance Patterns to ALS-inhibiting Herbicides of Catchweed Bedstraw (Galium aparine) with Different ALS Mutations

Weed Science ◽  
2018 ◽  
Vol 67 (2) ◽  
pp. 183-188 ◽  
Author(s):  
Wei Deng ◽  
Yingjie Di ◽  
Jingxuan Cai ◽  
Yueyang Chen ◽  
Shuzhong Yuan
Keyword(s):  
Acetolactate Synthase ◽  
Resistance Mechanisms ◽  
Target Site ◽  
Cross Resistance ◽  
Susceptible Population ◽  
Resistance Evolution ◽  
Galium Aparine ◽  
Resistance Patterns ◽  
Target Site Resistance ◽  
Tribenuron Methyl

AbstractCatchweed bedstraw (Galium aparine L.) is a problematic dicot weed that occurs in major winter wheat (Triticum aestivum L.) fields in China. Tribenuron-methyl has been widely used to control broadleaf weeds since 1988 in China. However, overuse has led to the resistance evolution of G. aparine to tribenuron-methyl. In this study, 20 G. aparine populations collected from Shandong and Henan provinces were used to determine tribenuron-methyl resistance and target-site resistance mechanisms. In dose–response experiments, 12 G. aparine populations showed different resistance levels (2.92 to 842.41-fold) to tribenuron-methyl compared with the susceptible population. Five different acetolactate synthase (ALS) mutations (Pro-197-Leu, Pro-197-Ser, Pro-197-His, Asp-376-Glu, and Trp-574-Leu) were detected in different resistant populations. Individuals heterozygous for Pro-197-Ser and Trp-574-Leu mutations were also observed in a resistant population (HN6). In addition, pHB4 (Pro-197-Ser), pHB7 (Pro-197-His), pHB8 (Pro-197-Leu), pHB5 (Asp-376-Glu), and pHB3 (Trp-574-Leu) subpopulations individually homozygous for specific ALS mutations were generated to evaluate the cross-resistance to ALS-inhibiting herbicides. The pHB4, pHB7, pHB8, pHB5, and pHB3 subpopulations all were resistant to sulfonylurea, pyrazosulfuron-ethyl, triazolopyrimidine, flumetsulam, sulfonylamino-carbonyl-triazolinone, flucarbazone-sodium, pyrimidinyl thiobenzoate, pyribenzoxim, and the imidazolinone imazethapyr. These results indicated the diversity of the resistance-conferring ALS mutations in G. aparine, and all these mutations resulted in broad cross-resistance to five kinds of ALS-inhibiting herbicides.

scholarly journals Insecticide resistance in field populations of the tomato fruitworm, Helicoverpa armigera, from Senegal

2020 ◽  
Vol 14 (1) ◽  
pp. 181-191
Author(s):  
Serigne Omar Sene ◽  
Etienne Tendeng ◽  
Mamadou Diatte ◽  
Serigne Sylla ◽  
Babacar Labou ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Helicoverpa Armigera ◽  
Cropping Systems ◽  
Resistance Mechanisms ◽  
Cross Resistance ◽  
Metabolic Resistance ◽  
Resistance Evolution ◽  
The North ◽  
Helicoverpa Armígera ◽  
Lepidoptera Noctuidae

Monitoring of the evolution of insecticide resistance in the field is crucial to prevent pest control issues. The present study was conducted to assess insecticide resistance status of the fruitworm, Helicoverpa armigera (Hübner) (Lepidoptera, Noctuidae), the most destructive pest of field-grown tomato in Senegal. A sample of 11- 15 field populations were monitored for their susceptibility to abamectin, deltamethrin, and profenofos, using a standard leaf-dip bioassay method. Resistance ratios ranged from 1- to 30-fold to abamectin (4/15 populations with RR>10), 7- to 112-fold to deltamethrin (11/12 populations with RR>10), and 1- to 29-fold to profenofos (3/11 populations with RR>10). This indicates that resistance evolution to deltamethrin was widespread among field populations of H. armigera. However, an increasing trend of resistance to deltamethrin was observed from the South to the North of Niayes. Susceptibility to abamectin and profenofos was generally high but showed that resistance might be evolving within some populations. In addition, signs of cross-resistance to abamectin were detected, suggesting possible metabolic resistance mechanisms already selected in pyrethroid-resistant populations. The recorded high levels of pyrethroids resistance are a concern for the control of H. armigera in Senegal as the country is being currently embarking into economic expansion of tomato cropping systems. © 2020 International Formulae Group. All rights reserved. Keywords: Insecticide resistance, pyrethroids, avermectins, OPs, Helicoverpa armigera, West Africa

Survey on the phage resistance mechanisms displayed by a dairy Lactobacillus helveticus strain

2017 ◽  
Vol 66 ◽  
pp. 110-116 ◽  
Author(s):  
Miriam Zago ◽  
Luigi Orrù ◽  
Lia Rossetti ◽  
Antonella Lamontanara ◽  
Maria Emanuela Fornasari ◽  
...  
Keyword(s):  
Resistance Mechanisms ◽  
Lactobacillus Helveticus ◽  
Phage Resistance

scholarly journals Simplified Approach to Predict Food Safety through the Maximum Specific Bacterial Growth Rate as Function of Extrinsic and Intrinsic Parameters

2021 ◽  
Vol 5 (2) ◽  
pp. 22
Author(s):  
Pedro D. Gaspar ◽  
Joel Alves ◽  
Pedro Pinto
Keyword(s):  
Growth Rate ◽  
Food Safety ◽  
Information And Communication Technologies ◽  
Bacterial Growth ◽  
Low Cost ◽  
Extrinsic Factors ◽  
Bacterial Growth Rate ◽  
Modeling Tools ◽  
Simplified Approach ◽  
Food Safety And Quality

Currently, we assist the emergence of sensors and low-cost information and communication technologies applied to food products, in order to improve food safety and quality along the food chain. Thus, it is relevant to implement predictive mathematical modeling tools in order to predict changes in the food quality and allow decision-making for expiration dates. To perform that, the Baranyi and Roberts model and the online tool Combined Database for Predictive Microbiology (Combase) were used to determine the factors that define the growth of different bacteria. These factors applied to the equation that determines the maximum specific growth rate establish a relation between the bacterial growth and the intrinsic and extrinsic factors that define the bacteria environment. These models may be programmed in low-cost wireless biochemical sensor devices applied to packaging and food supply chains to promote food safety and quality through real time traceability.

scholarly journals Phage Resistance Is Associated with Decreased Virulence in KPC-Producing Klebsiella pneumoniae of the Clonal Group 258 Clade II Lineage

2021 ◽  
Vol 9 (4) ◽  
pp. 762
Author(s):  
Lucia Henrici De Angelis ◽  
Noemi Poerio ◽  
Vincenzo Di Pilato ◽  
Federica De Santis ◽  
Alberto Antonelli ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Parental Strain ◽  
Bacterial Infections ◽  
Capsular Polysaccharide ◽  
Galleria Mellonella ◽  
Bacterial Pathogen ◽  
Phage Resistance ◽  
Infection Model ◽  
Lytic Phage ◽  
Susceptible Host

Phage therapy is now reconsidered with interest in the treatment of bacterial infections. A major piece of information for this application is the definition of the molecular targets exploited by phages to infect bacteria. Here, the genetic basis of resistance to the lytic phage φBO1E by its susceptible host Klebsiella pneumoniae KKBO-1 has been investigated. KKBO-1 phage-resistant mutants were obtained by infection at high multiplicity. One mutant, designated BO-FR-1, was selected for subsequent experiments, including virulence assessment in a Galleria mellonella infection model and characterization by whole-genome sequencing. Infection with BO-FR-1 was associated with a significantly lower mortality when compared to that of the parental strain. The BO-FR-1 genome differed from KKBO-1 by a single nonsense mutation into the wbaP gene, which encodes a glycosyltransferase involved in the first step of the biosynthesis of the capsular polysaccharide (CPS). Phage susceptibility was restored when BO-FR-1 was complemented with the constitutive wbaP gene. Our results demonstrated that φBO1E infects KKBO-1 targeting the bacterial CPS. Interestingly, BO-FR-1 was less virulent than the parental strain, suggesting that in the context of the interplay among phage, bacterial pathogen and host, the emergence of phage resistance may be beneficial for the host.

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