scholarly journals Cross-kingdom recognition of bacterial small RNAs induces transgenerational pathogenic avoidance

2019 ◽  
Author(s):  
Rachel Kaletsky ◽  
Rebecca S. Moore ◽  
Lance L. Parsons ◽  
Coleen T. Murphy

AbstractWe recently discovered that C. elegans can pass on a learned avoidance of pathogenic Pseudomonas aeruginosa (PA14) to four generations of its progeny. This transgenerational inheritance is bacterial species-specific, but how C. elegans recognizes and distinguishes different bacteria and transmits this information to future generations is not apparent. Here we show that small RNAs purified from pathogenic PA14 are sufficient not only to induce avoidance of pathogens in mothers, but also to confer transgenerational inheritance of this species-specific behavior for four generations, all without direct contact with pathogenic bacteria. This behavior requires the small RNA transporters SID-1 and SID-2, RNA interference pathway components, the piRNA Piwi/Argonaute pathway, a functioning germline, and TGF-β ligand daf-7 expression in the ASI sensory neuron. Our results suggest that C. elegans “reads” small RNAs expressed by pathogenic bacteria, and uses this information to induce an escape behavior that lasts for four additional generations. C. elegans may have evolved this trans-kingdom signaling system to avoid pathogens in abundant classes of bacteria in its environment and its microbiome.

2018 ◽  
Vol 84 (19) ◽  
Author(s):  
Yvonne Agersø ◽  
Birgitte Stuer-Lauridsen ◽  
Karin Bjerre ◽  
Michelle Geervliet Jensen ◽  
Eric Johansen ◽  
...  

ABSTRACTBacillus megaterium(n= 29),Bacillus velezensis(n= 26),Bacillus amyloliquefaciens(n= 6),Bacillus paralicheniformis(n= 28), andBacillus licheniformis(n= 35) strains from different sources, origins, and time periods were tested for the MICs for nine antimicrobial agents by the CLSI-recommended method (Mueller-Hinton broth, 35°C, for 18 to 20 h), as well as with a modified CLSI method (Iso-Sensitest [IST] broth, 37°C [35°C forB. megaterium], 24 h). This allows a proposal of species-specific epidemiological cutoff values (ECOFFs) for the interpretation of antimicrobial resistance in these species. MICs determined by the modified CLSI method were 2- to 16-fold higher than with the CLSI-recommended method for several antimicrobials. The MIC distributions differed between species for five of the nine antimicrobials. Consequently, use of the modified CLSI method and interpretation of resistance by use of species-specific ECOFFs is recommended. The genome sequences of all strains were determined and used for screening for resistance genes against the ResFinder database and for multilocus sequence typing. A putative chloramphenicol acetyltransferase (cat) gene was found in oneB. megateriumstrain with an elevated chloramphenicol MIC compared to the otherB. megateriumstrains. InB. velezensisandB. amyloliquefaciens, a putative tetracycline efflux gene,tet(L), was found in all strains (n= 27) with reduced tetracycline susceptibility but was absent in susceptible strains. AllB. paralicheniformisand 23% ofB. licheniformisstrains had elevated MICs for erythromycin and harboredermD. The presence of these resistance genes follows taxonomy suggesting they may be intrinsic rather than horizontally acquired. Reduced susceptibility to chloramphenicol, streptomycin, and clindamycin could not be explained in all species.IMPORTANCEWhen commercializing bacterial strains, likeBacillusspp., for feed applications or plant bioprotection, it is required that the strains are free of acquired antimicrobial resistance genes that could potentially spread to pathogenic bacteria, thereby adding to the pool of resistance genes that may cause treatment failures in humans or animals. Conversely, if antimicrobial resistance is intrinsic to a bacterial species, the risk of spreading horizontally to other bacteria is considered very low. Reliable susceptibility test methods and interpretation criteria at the species level are needed to accurately assess antimicrobial resistance levels. In the present study, tentative ECOFFs for fiveBacillusspecies were determined, and the results showed that the variation in MICs followed the respective species. Moreover, putative resistance genes, which were detected by whole-genome sequencing and suggested to be intrinsic rather that acquired, could explain the resistance phenotypes in most cases.


2020 ◽  
Author(s):  
Jamal Hussen

Abstract Background: Recent studies have reported pathogen-species-specific modulating effects on the innate immune system. Escherichia coli, Staphylococcus aureus, and Streptococcus agalactiae are important pathogenic bacteria responsible for different infectious diseases in several animal species. In the present study, a whole blood culture and flow cytometry were used to investigate, whether stimulation with different bacterial species induces different immunomodulation patterns in camel leukocytes. Results: Stimulation with either of the bacterial species resulted in the expansion of the camel CD14highMHCIIhigh monocyte subset with a reduced fraction of CD14highMHCIIlow monocytes. For the CD14highMHCIIlow monocytes, however, only stimulation with S. aureus or S. agalactiae increased their fractions in blood. Although all bacterial species elicited the upregulation of cell surface MHC-II molecules on granulocytes, the increase was, however, highest on cells stimulated with S. aureus. The expression levels of the two adhesion molecules, CD11a and CD18, on neutrophils and monocytes were differently affected by bacterial stimulation. Functionally, E. coli failed to stimulate ROS production in monocytes, while induced a strong ROS production response in granulocytes. S. agalactiae elicited a week ROS production in granulocytes when compared to the other two pathogens. Conclusions: The different responsiveness of monocytes and granulocytes toward different bacterial species indicates different host-pathogen interaction mechanisms for the two cell populations. In addition, the phenotypic and functional differences between cells stimulated with E. coli, S. aureus, or S. agalactiae suggests pathogen-species-specific modulating effects of the bacterial pathogens on the camel innate myeloid cells.


2019 ◽  
Author(s):  
Leah Houri-Ze’evi ◽  
Guy Teichman ◽  
Hila Gingold ◽  
Oded Rechavi

AbstractTransgenerational inheritance of small RNAs is challenging basic concepts of heredity and achieving control over such responses is of great interest. InC. elegansnematodes, small RNAs are transmitted across generations to establish a transgenerational memory trace of ancestral environments and distinguish self from non-self genes. Inheritance of small RNAs is regulated by dedicated machinery and carryover of aberrant heritable small RNA responses was shown to be maladaptive and to induce sterility. Here we show that various types of stress (starvation, high temperatures, and high osmolarity) but not non-stressful changes in cultivation conditions, lead to resetting of small RNA inheritance. We found that stress leads to a genome-wide reduction in heritable small RNA levels and that mutants defective in different stress pathways exhibit irregular RNAi inheritance dynamics. Moreover, we discovered that resetting of heritable RNAi is orchestrated by MAPK pathway factors, the transcription factor SKN-1, and the MET-2 methyltransferase. Termination of small RNA inheritance, and the fact that this process depends on stress, could protect from run-on of environment-irrelevant heritable gene regulation.


2008 ◽  
Vol 190 (11) ◽  
pp. 3896-3903 ◽  
Author(s):  
Shari E. Gelber ◽  
Jorge L. Aguilar ◽  
Kanako L. T. Lewis ◽  
Adam J. Ratner

ABSTRACT Pore-forming toxins are essential to the virulence of a wide variety of pathogenic bacteria. Gardnerella vaginalis is a bacterial species associated with bacterial vaginosis (BV) and its significant adverse sequelae, including preterm birth and acquisition of human immunodeficiency virus. G. vaginalis makes a protein toxin that generates host immune responses and has been hypothesized to be involved in the pathogenesis of BV. We demonstrate that G. vaginalis produces a toxin (vaginolysin [VLY]) that is a member of the cholesterol-dependent cytolysin (CDC) family, most closely related to intermedilysin from Streptococcus intermedius. Consistent with this predicted relationship, VLY lyses target cells in a species-specific manner, dependent upon the complement regulatory molecule CD59. In addition to causing erythrocyte lysis, VLY activates the conserved epithelial p38 mitogen-activated protein kinase pathway and induces interleukin-8 production by human epithelial cells. Transfection of human CD59 into nonsusceptible cells renders them sensitive to VLY-mediated lysis. In addition, a single amino acid substitution in the VLY undecapeptide [VLY(P480W)] generates a toxoid that does not form pores, and introduction of the analogous proline residue into another CDC, pneumolysin, significantly decreases its cytolytic activity. Further investigation of the mechanism of action of VLY may improve understanding of the functions of the CDC family as well as diagnosis and therapy for BV.


Cell ◽  
2014 ◽  
Vol 158 (2) ◽  
pp. 277-287 ◽  
Author(s):  
Oded Rechavi ◽  
Leah Houri-Ze’evi ◽  
Sarit Anava ◽  
Wee Siong Sho Goh ◽  
Sze Yen Kerk ◽  
...  

2006 ◽  
Vol 50 (4) ◽  
pp. 1480-1488 ◽  
Author(s):  
Randal Eckert ◽  
Fengxia Qi ◽  
Daniel K. Yarbrough ◽  
Jian He ◽  
Maxwell H. Anderson ◽  
...  

ABSTRACT Currently available antimicrobials exhibit broad killing with regard to bacterial genera and species. Indiscriminate killing of microbes by these conventional antibiotics can disrupt the ecological balance of the indigenous microbial flora, often resulting in negative clinical consequences. Species-specific antimicrobials capable of precisely targeting pathogenic bacteria without damaging benign microorganisms provide a means of avoiding this problem. In this communication, we report the successful creation of the first synthetic, target-specific antimicrobial peptide, G10KHc, via addition of a rationally designed Pseudomonas-specific targeting moiety (KH) to a generally killing peptide (novispirin G10). The resulting chimeric peptide showed enhanced bactericidal activity and faster killing kinetics against Pseudomonas spp. than G10 alone. The enhanced killing activities are due to increased binding and penetration of the outer membrane of Pseudomonas sp. cells. These properties were not observed in tests of untargeted bacterial species, and this specificity allowed G10KHc to selectively eliminate Pseudomonas spp. from mixed cultures. This work lays a foundation for generating target-specific “smart” antimicrobials to complement currently available conventional antibiotics.


2020 ◽  
Vol 32 (3) ◽  
pp. 413-419
Author(s):  
Godelind A. Wolf-Jäckel ◽  
Mette Boye ◽  
Øystein Angen ◽  
Matthias Müller ◽  
Tim K. Jensen

Campylobacter infection is a leading cause of ovine abortion worldwide. Campylobacter fetus and C. jejuni are the major species involved. We report herein on abortion storms in 4 Danish sheep flocks. Initially, no pathogenic bacteria were isolated from placental and fetal tissues on aerobic and selective media despite the presence of severe suppurative and necrotizing placentitis with numerous bacteria located intracellularly in trophoblasts. Fluorescence in situ hybridization (FISH) was then applied on abortion material from 13 cases; species-specific oligonucleotide probes directed against either C. fetus or C. jejuni were used in combination with a general bacterial probe. C. fetus was detected as the only lesion-associated bacterial species in 4 cases from 2 flocks, and C. jejuni in 6 cases from the other 2 flocks, thereby establishing the likely etiology of the abortion storms in all 4 flocks. FISH is a useful detection tool in culture-negative cases with tissue lesions suggestive of bacterial infection. Furthermore, FISH is a fast and economical method to detect and identify the zoonotic agent Campylobacter within ovine abortion material.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Leah Houri Zeevi ◽  
Guy Teichman ◽  
Hila Gingold ◽  
Oded Rechavi

Transgenerational inheritance of small RNAs challenges basic concepts of heredity. In C. elegans nematodes, small RNAs are transmitted across generations to establish a transgenerational memory trace of ancestral environments and distinguish self-genes from non-self-elements. Carryover of aberrant heritable small RNA responses was shown to be maladaptive and to lead to sterility. Here we show that various types of stress (starvation, high temperatures, and high osmolarity) induce resetting of ancestral small RNA responses and a genome-wide reduction in heritable small RNA levels. We found that mutants that are defective in various stress pathways exhibit irregular RNAi inheritance dynamics even in the absence of stress. Moreover, we discovered that resetting of ancestral RNAi responses is specifically orchestrated by factors that function in the p38 MAPK pathway and the transcription factor SKN-1/Nrf2. Stress-dependent termination of small RNA inheritance could protect from run-on of environment-irrelevant heritable gene regulation.


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