scholarly journals Lactobacillus spp. attenuate antibiotic-induced immune and microbiota dysregulation in honey bees

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Brendan A. Daisley ◽  
Andrew P. Pitek ◽  
John A. Chmiel ◽  
Shaeley Gibbons ◽  
Anna M. Chernyshova ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Honey Bees ◽  
Disease Burden ◽  
Efflux Pump ◽  
Antibiotic Administration ◽  
Nutrient Metabolism ◽  
Xenobiotic Exposure ◽  
Environmental Xenobiotic ◽  
Bee Disease ◽  
Lactobacillus Spp

Abstract Widespread antibiotic usage in apiculture contributes substantially to the global dissemination of antimicrobial resistance and has the potential to negatively influence bacterial symbionts of honey bees (Apis mellifera). Here, we show that routine antibiotic administration with oxytetracycline selectively increased tetB (efflux pump resistance gene) abundance in the gut microbiota of adult workers while concurrently depleting several key symbionts known to regulate immune function and nutrient metabolism such as Frischella perrera and Lactobacillus Firm-5 strains. These microbial changes were functionally characterized by decreased capped brood counts (marker of hive nutritional status and productivity) and reduced antimicrobial capacity of adult hemolymph (indicator of immune competence). Importantly, combination therapy with three immunostimulatory Lactobacillus strains could mitigate antibiotic-associated microbiota dysbiosis and immune deficits in adult workers, as well as maximize the intended benefit of oxytetracycline by suppressing larval pathogen loads to near-undetectable levels. We conclude that microbial-based therapeutics may offer a simple but effective solution to reduce honey bee disease burden, environmental xenobiotic exposure, and spread of antimicrobial resistance.

scholarly journals Antibiotic Resistance Markers in Burkholderia pseudomallei Strain Bp1651 Identified by Genome Sequence Analysis

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Julia V. Bugrysheva ◽  
David Sue ◽  
Jay E. Gee ◽  
Mindy G. Elrod ◽  
Alex R. Hoffmaster ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Clavulanic Acid ◽  
Burkholderia Pseudomallei ◽  
Efflux Pump ◽  
Point Mutations ◽  
Comparative Genomic ◽  
Content Type ◽  
Reductase Gene ◽  
Amoxicillin Clavulanic Acid ◽  
Imipenem Resistance

ABSTRACT Burkholderia pseudomallei Bp1651 is resistant to several classes of antibiotics that are usually effective for treatment of melioidosis, including tetracyclines, sulfonamides, and β-lactams such as penicillins (amoxicillin-clavulanic acid), cephalosporins (ceftazidime), and carbapenems (imipenem and meropenem). We sequenced, assembled, and annotated the Bp1651 genome and analyzed the sequence using comparative genomic analyses with susceptible strains, keyword searches of the annotation, publicly available antimicrobial resistance prediction tools, and published reports. More than 100 genes in the Bp1651 sequence were identified as potentially contributing to antimicrobial resistance. Most notably, we identified three previously uncharacterized point mutations in penA, which codes for a class A β-lactamase and was previously implicated in resistance to β-lactam antibiotics. The mutations result in amino acid changes T147A, D240G, and V261I. When individually introduced into select agent-excluded B. pseudomallei strain Bp82, D240G was found to contribute to ceftazidime resistance and T147A contributed to amoxicillin-clavulanic acid and imipenem resistance. This study provides the first evidence that mutations in penA may alter susceptibility to carbapenems in B. pseudomallei. Another mutation of interest was a point mutation affecting the dihydrofolate reductase gene folA, which likely explains the trimethoprim resistance of this strain. Bp1651 was susceptible to aminoglycosides likely because of a frameshift in the amrB gene, the transporter subunit of the AmrAB-OprA efflux pump. These findings expand the role of penA to include resistance to carbapenems and may assist in the development of molecular diagnostics that predict antimicrobial resistance and provide guidance for treatment of melioidosis.

scholarly journals The carbon source influences the efflux pump-mediated antimicrobial resistance in clinically important Gram-negative bacteria

2012 ◽  
Vol 67 (4) ◽  
pp. 921-927 ◽  
Author(s):  
N. A. Villagra ◽  
J. A. Fuentes ◽  
M. R. Jofre ◽  
A. A. Hidalgo ◽  
P. Garcia ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Carbon Source ◽  
Efflux Pump ◽  
Gram Negative Bacteria ◽  
Gram Negative

scholarly journals Response of Staphylococcus aureus to Salicylate Challenge

2006 ◽  
Vol 189 (1) ◽  
pp. 220-227 ◽  
Author(s):  
James T. Riordan ◽  
Arunachalam Muthaiyan ◽  
Wayne Van Voorhies ◽  
Christopher T. Price ◽  
James E. Graham ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Resistance ◽  
Transcriptome Analysis ◽  
Target Genes ◽  
Efflux Pump ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Antibiotic Target ◽  
Unique Mechanism ◽  
Formate Metabolism

ABSTRACT Growth of Staphylococcus aureus with the nonsteroidal anti-inflammatory salicylate reduces susceptibility of the organism to multiple antimicrobials. Transcriptome analysis revealed that growth of S. aureus with salicylate leads to the induction of genes involved with gluconate and formate metabolism and represses genes required for gluconeogenesis and glycolysis. In addition, salicylate induction upregulates two antibiotic target genes and downregulates a multidrug efflux pump gene repressor (mgrA) and sarR, which represses a gene (sarA) important for intrinsic antimicrobial resistance. We hypothesize that these salicylate-induced alterations jointly represent a unique mechanism that allows S. aureus to resist antimicrobial stress and toxicity.

scholarly journals Silencing the Honey Bee (Apis mellifera) Naked Cuticle Gene (nkd) Improves Host Immune Function and Reduces Nosema ceranae Infections

2016 ◽  
Vol 82 (22) ◽  
pp. 6779-6787 ◽  
Author(s):  
Wenfeng Li ◽  
Jay D. Evans ◽  
Qiang Huang ◽  
Cristina Rodríguez-García ◽  
Jie Liu ◽  
...  
Keyword(s):  
Apis Mellifera ◽  
Immune Function ◽  
Honey Bee ◽  
Honey Bees ◽  
Nosema Ceranae ◽  
Negative Regulator ◽  
Mrna Levels ◽  
Content Type ◽  
Bee Disease

ABSTRACTNosema ceranaeis a new and emerging microsporidian parasite of European honey bees,Apis mellifera, that has been implicated in colony losses worldwide. RNA interference (RNAi), a posttranscriptional gene silencing mechanism, has emerged as a potent and specific strategy for controlling infections of parasites and pathogens in honey bees. While previous studies have focused on the silencing of parasite/pathogen virulence factors, we explore here the possibility of silencing a host factor as a mechanism for reducing parasite load. Specifically, we used an RNAi strategy to reduce the expression of a honey bee gene,naked cuticle(nkd), which is a negative regulator of host immune function. Our studies found thatnkdmRNA levels in adult bees were upregulated byN. ceranaeinfection (and thus, the parasite may use this mechanism to suppress host immune function) and that ingestion of double-stranded RNA (dsRNA) specific tonkdefficiently silenced its expression. Furthermore, we found that RNAi-mediated knockdown ofnkdtranscripts inNosema-infected bees resulted in upregulation of the expression of several immune genes (Abaecin,Apidaecin,Defensin-1, andPGRP-S2), reduction ofNosemaspore loads, and extension of honey bee life span. The results of our studies clearly indicate that silencing the hostnkdgene can activate honey bee immune responses, suppress the reproduction ofN. ceranae, and improve the overall health of honey bees. This study represents a novel host-derived therapeutic for honey bee disease treatment that merits further exploration.IMPORTANCEGiven the critical role of honey bees in the pollination of agricultural crops, it is urgent to develop strategies to prevent the colony decline induced by the infection of parasites/pathogens. Targeting parasites and pathogens directly by RNAi has been proven to be useful for controlling infections in honey bees, but little is known about the disease impacts of RNAi silencing of host factors. Here, we demonstrate that knocking down the honey bee immune repressor-encodingnkdgene can suppress the reproduction ofN. ceranaeand improve the overall health of honey bees, which highlights the potential role of host-derived and RNAi-based therapeutics in controlling the infections in honey bees. The information obtained from this study will have positive implications for honey bee disease management practices.

scholarly journals An In Vitro Chicken Gut Model Demonstrates Transfer of a Multidrug Resistance Plasmid from Salmonella to Commensal Escherichia coli

mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Roderick M. Card ◽  
Shaun A. Cawthraw ◽  
Javier Nunez-Garcia ◽  
Richard J. Ellis ◽  
Gemma Kay ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Gastrointestinal Tract ◽  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Animal Health ◽  
Plasmid Transfer ◽  
High Rate ◽  
Antibiotic Administration

ABSTRACT The chicken gastrointestinal tract is richly populated by commensal bacteria that fulfill various beneficial roles for the host, including helping to resist colonization by pathogens. It can also facilitate the conjugative transfer of multidrug resistance (MDR) plasmids between commensal and pathogenic bacteria which is a significant public and animal health concern as it may affect our ability to treat bacterial infections. We used an in vitro chemostat system to approximate the chicken cecal microbiota, simulate colonization by an MDR Salmonella pathogen, and examine the dynamics of transfer of its MDR plasmid harboring several genes, including the extended-spectrum beta-lactamase bla CTX-M1. We also evaluated the impact of cefotaxime administration on plasmid transfer and microbial diversity. Bacterial community profiles obtained by culture-independent methods showed that Salmonella inoculation resulted in no significant changes to bacterial community alpha diversity and beta diversity, whereas administration of cefotaxime caused significant alterations to both measures of diversity, which largely recovered. MDR plasmid transfer from Salmonella to commensal Escherichia coli was demonstrated by PCR and whole-genome sequencing of isolates purified from agar plates containing cefotaxime. Transfer occurred to seven E. coli sequence types at high rates, even in the absence of cefotaxime, with resistant strains isolated within 3 days. Our chemostat system provides a good representation of bacterial interactions, including antibiotic resistance transfer in vivo. It can be used as an ethical and relatively inexpensive approach to model dissemination of antibiotic resistance within the gut of any animal or human and refine interventions that mitigate its spread before employing in vivo studies. IMPORTANCE The spread of antimicrobial resistance presents a grave threat to public health and animal health and is affecting our ability to respond to bacterial infections. Transfer of antimicrobial resistance via plasmid exchange is of particular concern as it enables unrelated bacteria to acquire resistance. The gastrointestinal tract is replete with bacteria and provides an environment for plasmid transfer between commensals and pathogens. Here we use the chicken gut microbiota as an exemplar to model the effects of bacterial infection, antibiotic administration, and plasmid transfer. We show that transfer of a multidrug-resistant plasmid from the zoonotic pathogen Salmonella to commensal Escherichia coli occurs at a high rate, even in the absence of antibiotic administration. Our work demonstrates that the in vitro gut model provides a powerful screening tool that can be used to assess and refine interventions that mitigate the spread of antibiotic resistance in the gut before undertaking animal studies. IMPORTANCE The spread of antimicrobial resistance presents a grave threat to public health and animal health and is affecting our ability to respond to bacterial infections. Transfer of antimicrobial resistance via plasmid exchange is of particular concern as it enables unrelated bacteria to acquire resistance. The gastrointestinal tract is replete with bacteria and provides an environment for plasmid transfer between commensals and pathogens. Here we use the chicken gut microbiota as an exemplar to model the effects of bacterial infection, antibiotic administration, and plasmid transfer. We show that transfer of a multidrug-resistant plasmid from the zoonotic pathogen Salmonella to commensal Escherichia coli occurs at a high rate, even in the absence of antibiotic administration. Our work demonstrates that the in vitro gut model provides a powerful screening tool that can be used to assess and refine interventions that mitigate the spread of antibiotic resistance in the gut before undertaking animal studies.

scholarly journals Involvement of the AcrAB-TolC Efflux Pump in the Resistance, Fitness, and Virulence of Enterobacter cloacae

2012 ◽  
Vol 56 (4) ◽  
pp. 2084-2090 ◽  
Author(s):  
Astrid Pérez ◽  
Margarita Poza ◽  
Ana Fernández ◽  
Maria del Carmen Fernández ◽  
Susana Mallo ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Pathogenic Bacteria ◽  
Efflux Pump ◽  
Enterobacter Cloacae ◽  
Efflux Pumps ◽  
Clinical Isolates ◽  
Wild Type ◽  
Content Type

ABSTRACTMultidrug efflux pumps have emerged as important mechanisms of antimicrobial resistance in bacterial pathogens. In order to cause infection, pathogenic bacteria require mechanisms to avoid the effects of host-produced compounds, and express efflux pumps may accomplish this task. In this study, we evaluated the effect of the inactivation of AcrAB-TolC on antimicrobial resistance, fitness, and virulence inEnterobacter cloacae, an opportunistic pathogen usually involved in nosocomial infections. Two different clinical isolates ofE. cloacaewere used, EcDC64 (multidrug resistance overexpressing the AcrAB-TolC efflux pump) and Jc194 (basal AcrAB-TolC expression). TheacrAandtolCgenes were deleted in strains EcDC64 and Jc194 to produce, respectively, EcΔacrAand EcΔtolCand JcΔacrAand JcΔtolCknockout (KO) derivatives. Antibiotic susceptibility testing was performed with all isolates, and we discovered that these mechanisms are involved in the resistance ofE. cloacaeto several antibiotics. Competition experiments were also performed with wild-type and isogenic KO strains. The competition index (CI), defined as the mutant/wild-type ratio, revealed that theacrAandtolCgenes both affect the fitness ofE. cloacae, as fitness was clearly reduced in theacrAandtolCKO strains. The median CI values obtainedin vitroandin vivowere, respectively, 0.42 and 0.3 for EcDC64/EcΔacrA, 0.24 and 0.38 for EcDC64/EcΔtolC, 0.15 and 0.11 for Jc194/JcΔacrA, and 0.38 and 0.39 for Jc194/JcΔtolC. Use of an intraperitoneal mouse model of systemic infection revealed reduced virulence in bothE. cloacaeclinical strains when either theacrAortolCgene was inactivated. In conclusion, the structural components of the AcrAB-TolC efflux pump appear to play a role in antibiotic resistance as well as environmental adaptation and host virulence in clinical isolates ofE. cloacae.

scholarly journals Impacts of Diverse Natural Products on Honey Bee Viral Loads and Health

2021 ◽  
Vol 11 (22) ◽  
pp. 10732
Author(s):  
Dawn L. Boncristiani ◽  
James P. Tauber ◽  
Evan C. Palmer-Young ◽  
Lianfei Cao ◽  
William Collins ◽  
...  
Keyword(s):  
Natural Products ◽  
Immune Responses ◽  
Honey Bee ◽  
Honey Bees ◽  
Food Sources ◽  
Deformed Wing Virus ◽  
Bee Health ◽  
Honey Bee Health ◽  
Living Organisms ◽  
Bee Disease

Western honey bees (Apis mellifera), a cornerstone to crop pollination in the U.S., are faced with an onslaught of challenges from diseases caused by parasites, pathogens, and pests that affect this economically valuable pollinator. Natural products (NPs), produced by living organisms, including plants and microorganisms, can support health and combat disease in animals. NPs include both native extracts and individual compounds that can reduce disease impacts by supporting immunity or directly inhibiting pathogens, pests, and parasites. Herein, we describe the screening of NPs in laboratory cage studies for their effects on honey bee disease prevention and control. Depending on the expected activity of compounds, we measured varied responses, including viral levels, honey bee immune responses, and symbiotic bacteria loads. Of the NPs screened, several compounds demonstrated beneficial activities in honey bees by reducing levels of the critical honey bee virus deformed wing virus (DWV-A and-B), positively impacting the gut microbiome or stimulating honey bee immune responses. Investigations of the medicinal properties of NPs in honey bees will contribute to a better understanding of their potential to support honey bee immunity to fight off pests and pathogens and promote increased overall honey bee health. These investigations will also shed light on the ecological interactions between pollinators and specific floral food sources.

scholarly journals ToxR mediates the antivirulence activity of phenyl-arginine-β-naphthylamide to attenuate Vibrio cholerae virulence.

2021 ◽  
Author(s):  
Yuding Weng ◽  
Thomas F. Bina ◽  
X. Renee Bina ◽  
James E. Bina
Keyword(s):  
Antimicrobial Resistance ◽  
Vibrio Cholerae ◽  
Virulence Factor ◽  
Efflux Pump ◽  
Feedback Mechanism ◽  
Gram Negative ◽  
Factor Production ◽  
Regulatory Circuit ◽  
Efflux Pump Inhibitors ◽  
Virulence Factor Production

Multidrug efflux systems belonging to the resistance-nodulation-cell division (RND) family are ubiquitous in Gram negative bacteria and critical for antimicrobial resistance. This realization has led to efforts to develop efflux pump inhibitors (EPI) for use as adjuvants for antibiotic treatment of resistant organisms. However, the functions of RND transporters extend beyond antimicrobial resistance to include physiological functions that are critical for pathogenesis, suggesting that EPIs could also be used as antivirulence therapeutics. This was documented in the enteric pathogen Vibrio cholerae where EPIs were shown to attenuate the production of the critical virulence factors cholera toxin (CT) and the toxin coregulated pilus (TCP). In this study we investigated the antivirulence mechanism of action of the EPI phenyl-arginine-β-naphthylamide (PAβN) on V. cholerae. Using bioassays, we documented that PAβN inhibited virulence factor production in three epidemic V. cholerae isolates. Transcriptional reporter studies and mutant analysis indicated that PAβN initiated a ToxR-dependent regulatory circuit to activate leuO expression and that LeuO repressed the expression of the critical virulence activator aphA to attenuate CT and TCP production. The antivirulence activity of PAβN was found to be dependent on the ToxR periplasmic sensing domain suggesting that a feedback mechanism was involved in its activity. Collectively the data indicated that PAβN inhibited V. cholerae virulence factor production by activating a ToxR-dependent metabolic feedback mechanism to repress the expression of the ToxR virulence regulon. This suggests that efflux pump inhibitors could be used as antivirulence therapeutics for the treatment of cholera and perhaps other gram negative pathogens.

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