scholarly journals The distribution of plasmid fitness effects explains plasmid persistence in bacterial communities

2020 ◽  
Author(s):  
Aida Alonso-del Valle ◽  
Ricardo León-Sampedro ◽  
Jerónimo Rodríguez-Beltrán ◽  
Javier DelaFuente ◽  
Marta Hernández-García ◽  
...  

Introductory paragraphPlasmid persistence in bacterial populations is strongly influenced by the fitness effects associated with plasmid carriage. However, plasmid fitness effects in wild-type bacterial hosts remain largely unexplored. In this study, we determined the distribution of fitness effects (DFE) for the major antibiotic resistance plasmid pOXA-48 in wild-type, ecologically compatible enterobacterial isolates from the human gut microbiota. Our results show that although pOXA-48 produced an overall reduction in bacterial fitness, the DFE was dominated by quasi-neutral effects, and beneficial effects were observed in several isolates. Incorporating these data into a simple population dynamics model revealed a new set of conditions for plasmid stability in bacterial communities, with plasmid persistence increasing with bacterial diversity and becoming less dependent on conjugation. Moreover, genomic results showed a link between plasmid fitness effects and bacterial phylogeny, helping to explain pOXA-48 epidemiology. Our results provide a simple and general explanation for plasmid persistence in natural bacterial communities.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aida Alonso-del Valle ◽  
Ricardo León-Sampedro ◽  
Jerónimo Rodríguez-Beltrán ◽  
Javier DelaFuente ◽  
Marta Hernández-García ◽  
...  

AbstractPlasmid persistence in bacterial populations is strongly influenced by the fitness effects associated with plasmid carriage. However, plasmid fitness effects in wild-type bacterial hosts remain largely unexplored. In this study, we determined the fitness effects of the major antibiotic resistance plasmid pOXA-48_K8 in wild-type, ecologically compatible enterobacterial isolates from the human gut microbiota. Our results show that although pOXA-48_K8 produced an overall reduction in bacterial fitness, it produced small effects in most bacterial hosts, and even beneficial effects in several isolates. Moreover, genomic results showed a link between pOXA-48_K8 fitness effects and bacterial phylogeny, helping to explain plasmid epidemiology. Incorporating our fitness results into a simple population dynamics model revealed a new set of conditions for plasmid stability in bacterial communities, with plasmid persistence increasing with bacterial diversity and becoming less dependent on conjugation. These results help to explain the high prevalence of plasmids in the greatly diverse natural microbial communities.


2019 ◽  
Vol 6 (12) ◽  
pp. 191669 ◽  
Author(s):  
Henry Goehlich ◽  
Olivia Roth ◽  
Carolin C. Wendling

Being non-lytic, filamentous phages can replicate at high frequencies and often carry virulence factors, which are important in the evolution and emergence of novel pathogens. However, their net effect on bacterial fitness remains unknown. To understand the ecology and evolution between filamentous phages and their hosts, it is important to assess (i) fitness effects of filamentous phages on their hosts and (ii) how these effects depend on the environment. To determine how the net effect on bacterial fitness by filamentous phages changes across environments, we constructed phage–bacteria infection networks at ambient 15 practical salinity units (PSU) and stressful salinities (11 and 7 PSU) using the marine bacterium, Vibrio alginolyticus and its derived filamentous phages as model system. We observed no significant difference in network structure at 15 and 11 PSU. However, at 7 PSU phages significantly reduced bacterial growth changing network structure. This pattern was mainly driven by a significant increase in bacterial susceptibility. Our findings suggest that filamentous phages decrease bacterial growth, an indirect measure of fitness in stressful environmental conditions, which might impact bacterial communities, alter horizontal gene transfer events and possibly favour the emergence of novel pathogens in environmental Vibrios .


Genetics ◽  
2003 ◽  
Vol 163 (4) ◽  
pp. 1519-1526 ◽  
Author(s):  
H Allen Orr

AbstractWe know little about the distribution of fitness effects among new beneficial mutations, a problem that partly reflects the rarity of these changes. Surprisingly, though, population genetic theory allows us to predict what this distribution should look like under fairly general assumptions. Using extreme value theory, I derive this distribution and show that it has two unexpected properties. First, the distribution of beneficial fitness effects at a gene is exponential. Second, the distribution of beneficial effects at a gene has the same mean regardless of the fitness of the present wild-type allele. Adaptation from new mutations is thus characterized by a kind of invariance: natural selection chooses from the same spectrum of beneficial effects at a locus independent of the fitness rank of the present wild type. I show that these findings are reasonably robust to deviations from several assumptions. I further show that one can back calculate the mean size of new beneficial mutations from the observed mean size of fixed beneficial mutations.


2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 213-215
Author(s):  
K Madsen ◽  
H Dang ◽  
N Hotte ◽  
V Mocanu ◽  
M Ferdaoussi ◽  
...  

Abstract Background Empagliflozin (EMPA) is a highly selective sodium glucose cotransporter-2 (SGLT2) inhibitor and is increasingly being utilized as an antihyperglycemic agent in the management of type 2 diabetes. Interestingly, it has been demonstrated in human trials that EMPA treatment exerts potent cardioprotective effects by reducing cardiac inflammation independently of glycemic control. Further, EMPA has also been shown to suppress LPS-induced renal and systemic inflammation in an animal model. Based on these findings, we hypothesized that EMPA treatment may also be effective in reducing gut inflammation. Aims The aim of this study was to examine the effects of treatment with EMPA on gastrointestinal inflammation in an animal model of inflammatory bowel disease and to determine mechanistic insights regarding its direct effects on gut cytokine secretion. Methods Adult male and female IL-10-/- mice with established colitis were treated with a daily gavage of EMPA (10mg/kg; n=10) or vehicle (n=10) for 14 days. Disease activity was assessed by measurement of mouse weight, colonic weight and length, histological score, cytokine levels in colonic homogenate and lipocalin-2 levels in stool. To examine for possible direct effects of EMPA, colonic explants from wild-type (n=8) and IL-10-/- (n=8) mice were incubated with increasing doses of EMPA (0.1–5 µM) ± LPS (10µg/ml) for 2 hours and tissue levels of IL-1β and TNFα protein measured by ELISA. Results After 14 days EMPA treated IL-10-/- mice had a significant improvement in colonic inflammation as evidenced by decreased colonic weight to length ratio (p=0.019), decreased fecal lipocalin-2 (p=0.03), as well as decreased enterocyte injury (p=0.01), decreased lamina propria neutrophils (p=0.01) and decreased total histological score (p=0.006). EMPA treated mice also maintained their weight over the 14 days while untreated mice continued to lose weight (p=0.04). There were no significant differences in colonic homogenate levels of TNFα, IL-1β, or IL-6 or in blood glucose levels between EMPA-treated mice and controls. In addition, EMPA did not suppress levels of basal or LPS-induced TNFα and IL-1β in colonic explants from either wild-type or IL-10-/- mice suggesting that the beneficial effects in IL-10-/- mice were not due to direct effects of EMPA on colonic TNFα or IL-1β cytokine levels. Conclusions EMPA treatment dramatically improved histologic and fecal inflammatory markers and maintained body weight in adult IL-10-/- mice with established colitis. These findings suggest further investigations into the effects of EMPA in treating gut inflammation are warranted. Funding Agencies CAG, CIHR


2010 ◽  
Vol 77 (1) ◽  
pp. 258-268 ◽  
Author(s):  
Gustavo A. Romero-Pérez ◽  
Kim H. Ominski ◽  
Tim A. McAllister ◽  
Denis O. Krause

ABSTRACTFeces from cattle production are considered important sources of bacterial contamination of food and the environment. Little is known about the combined effects of arctic temperatures and fodder tannins on rumen and hindgut bacterial populations. Individual rumen liquor and rectal fecal samples from donor steers fed either alfalfa silage or sainfoin (Onobrychis viciifoliaScop.) silage and waterad libitumwere collected weekly on the first three sampling days and fortnightly afterwards. The daily ambient temperatures were registered and averaged to weekly mean temperatures. Steers fed sainfoin silage had lower (P< 0.05) concentrations of branched-chain volatile fatty acids (VFA) than those fed alfalfa silage. All VFA concentrations were higher (P< 0.001) in rumen liquor samples than in fecal samples. The interaction of sample type and diet showed a significant effect (P< 0.05) on the proportions of the bacterial community that were from the phylaProteobacteriaandVerrucomicrobia.Ambient temperature had an indirect effect (P< 0.05) on the phylumFirmicutes, as it affected its proportional balance. The bacterial population diversity in samples appeared to decrease concurrently with the ambient temperature. The phylumFirmicutesexplained the first principal component at 64.83 and 42.58% of the total variance in rumen liquor and fecal samples, respectively. The sample type had a larger effect on bacterial communities than diet and temperature. Certain bacterial populations seemed to be better adapted than others to environmentally adverse conditions, such as less access time to nutrients due to higher motility and rate of passage of digesta caused by extreme temperatures, or antimicrobials such as tannins, possibly due to an influence of their biogeographical location within the gut.


mSystems ◽  
2018 ◽  
Vol 3 (5) ◽  
Author(s):  
Johannes Cairns ◽  
Katariina Koskinen ◽  
Reetta Penttinen ◽  
Tommi Patinen ◽  
Anna Hartikainen ◽  
...  

ABSTRACTMobile genetic elements such as conjugative plasmids are responsible for antibiotic resistance phenotypes in many bacterial pathogens. The ability to conjugate, the presence of antibiotics, and ecological interactions all have a notable role in the persistence of plasmids in bacterial populations. Here, we set out to investigate the contribution of these factors when the conjugation network was disturbed by a plasmid-dependent bacteriophage. Phage alone effectively caused the population to lose plasmids, thus rendering them susceptible to antibiotics. Leakiness of the antibiotic resistance mechanism allowing Black Queen evolution (i.e. a “race to the bottom”) was a more significant factor than the antibiotic concentration (lethal vs sublethal) in determining plasmid prevalence. Interestingly, plasmid loss was also prevented by protozoan predation. These results show that outcomes of attempts to resensitize bacterial communities by disrupting the conjugation network are highly dependent on ecological factors and resistance mechanisms.IMPORTANCEBacterial antibiotic resistance is often a part of mobile genetic elements that move from one bacterium to another. By interfering with the horizontal movement and the maintenance of these elements, it is possible to remove the resistance from the population. Here, we show that a so-called plasmid-dependent bacteriophage causes the initially resistant bacterial population to become susceptible to antibiotics. However, this effect is efficiently countered when the system also contains a predator that feeds on bacteria. Moreover, when the environment contains antibiotics, the survival of resistance is dependent on the resistance mechanism. When bacteria can help their contemporaries to degrade antibiotics, resistance is maintained by only a fraction of the community. On the other hand, when bacteria cannot help others, then all bacteria remain resistant. The concentration of the antibiotic played a less notable role than the antibiotic used. This report shows that the survival of antibiotic resistance in bacterial communities represents a complex process where many factors present in real-life systems define whether or not resistance is actually lost.


2000 ◽  
Vol 279 (3) ◽  
pp. H1071-H1078 ◽  
Author(s):  
R. Ray Morrison ◽  
Rachael Jones ◽  
Anne M. Byford ◽  
Alyssa R. Stell ◽  
Jason Peart ◽  
...  

The role of A1adenosine receptors (A1AR) in ischemic preconditioning was investigated in isolated crystalloid-perfused wild-type and transgenic mouse hearts with increased A1AR. The effect of preconditioning on postischemic myocardial function, lactate dehydrogenase (LDH) release, and infarct size was examined. Functional recovery was greater in transgenic versus wild-type hearts (44.8 ± 3.4% baseline vs. 25.6 ± 1.7%). Preconditioning improved functional recovery in wild-type hearts from 25.6 ± 1.7% to 37.4 ± 2.2% but did not change recovery in transgenic hearts (44.8 ± 3.4% vs. 44.5 ± 3.9%). In isovolumically contracting hearts, pretreatment with selective A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine attenuated the improved functional recovery in both wild-type preconditioned (74.2 ± 7.3% baseline rate of pressure development over time untreated vs. 29.7 ± 7.3% treated) and transgenic hearts (84.1 ± 12.8% untreated vs. 42.1 ± 6.8% treated). Preconditioning wild-type hearts reduced LDH release (from 7,012 ± 1,451 to 1,691 ± 1,256 U · l−1 · g−1 · min−1) and infarct size (from 62.6 ± 5.1% to 32.3 ± 11.5%). Preconditioning did not affect LDH release or infarct size in hearts overexpressing A1AR. Compared with wild-type hearts, A1AR overexpression markedly reduced LDH release (from 7,012 ± 1,451 to 917 ± 1,123 U · l−1 · g−1 · min−1) and infarct size (from 62.6 ± 5.1% to 6.5 ± 2.1%). These data demonstrate that murine preconditioning involves endogenous activation of A1AR. The beneficial effects of preconditioning and A1AR overexpression are not additive. Taken with the observation that A1AR blockade equally eliminates the functional protection resulting from both preconditioning and transgenic A1AR overexpression, we conclude that the two interventions affect cardioprotection via common mechanisms or pathways.


2008 ◽  
Vol 52 (7) ◽  
pp. 2340-2345 ◽  
Author(s):  
Joanna E. Mroczkowska ◽  
Miriam Barlow

ABSTRACT bla TEM-1 expression results in penicillin resistance, whereas expression of many bla TEM-1 descendants, called extended-spectrum β-lactamases (ESBLs), results simultaneously in resistance to penicillins and extended-spectrum cephalosporins. Despite the expanded resistance phenotypes conferred by many ESBLs, bla TEM-1 is still the most abundant bla TEM allele in many microbial populations. This study examines the fitness effects of the two amino acid substitutions, R164S and E240K, that have occurred repeatedly among ESBL bla TEM-1 descendants. Using a single-nucleotide polymorphism-specific real-time quantitative PCR method, we analyzed the fitness of strains expressing bla TEM-1, bla TEM-10, and bla TEM-12. Our results show that bacteria expressing the ancestral bla TEM-1 allele have a fitness advantage over those expressing either bla TEM-10 or bla TEM-12 when exposed to ampicillin. This observation, combined with the fact that penicillins are the most prevalent antimicrobials prescribed worldwide, may explain why bla TEM-1 has persisted as the most frequently encountered bla TEM allele in bacterial populations.


2014 ◽  
Vol 11 (93) ◽  
pp. 20131071 ◽  
Author(s):  
Nina Alphey ◽  
Michael B. Bonsall

Some proposed genetics-based vector control methods aim to suppress or eliminate a mosquito population in a similar manner to the sterile insect technique. One approach under development in Anopheles mosquitoes uses homing endonuclease genes (HEGs)—selfish genetic elements (inherited at greater than Mendelian rate) that can spread rapidly through a population even if they reduce fitness. HEGs have potential to drive introduced traits through a population without large-scale sustained releases. The population genetics of HEG-based systems has been established using discrete-time mathematical models. However, several ecologically important aspects remain unexplored. We formulate a new continuous-time (overlapping generations) combined population dynamic and genetic model and apply it to a HEG that targets and knocks out a gene that is important for survival. We explore the effects of density dependence ranging from undercompensating to overcompensating larval competition, occurring before or after HEG fitness effects, and consider differences in competitive effect between genotypes (wild-type, heterozygotes and HEG homozygotes). We show that population outcomes—elimination, suppression or loss of the HEG—depend crucially on the interaction between these ecological aspects and genetics, and explain how the HEG fitness properties, the homing rate (drive) and the insect's life-history parameters influence those outcomes.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Juan F. Alzate ◽  
Miguel Toro-Londoño ◽  
Felipe Cabarcas ◽  
Gisela Garcia-Montoya ◽  
Ana Galvan-Diaz

Abstract Recent studies have shown how intestinal parasites can modulate gut microbiota. This observation is not surprising since the human intestinal lumen, like any other niche, is a battlefield of microbial competition, and Eukaryotes can affect bacterial populations. Intestinal pathogenic protist has been associated with reshaping the microbial community structure; however, the interactions between the colonic bacterial communities and parasites like Blastocystis spp., Entamoeba coli, and Endolimax nana have been poorly studied. In this work, we studied the distal intestinal bacterial microbiota of 49 children attending 7 public daycare centers in Medellin, Colombia, and compared the bacterial microbiota structure in the presence or absence of the protists Blastocystis spp., E. coli, and E. nana. Parasite colonization was associated with an increase in bacterial richness. Moreover, Blastocystis spp. presented a positive relationship with Prevotella, since this bacterium was selectively enriched in children carrying it. Remarkably, the E. coli colonized children showed a microbial profile that was closer to uninfected controls, although some bacterial taxa displayed to be enriched. This is the case for Akkermansia, which showed to be favored in E. coli colonized individuals, while notably reduced in the Blastocystis spp. parasitized group.


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