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Factors influencing horizontal gene transfer in the intestine

Published online by Cambridge University Press:  18 April 2018

Ximin Zeng
Department of Animal Science, The University of Tennessee, 2506 River Drive, Knoxville, TN 37996-4574, USA
Jun Lin*
Department of Animal Science, The University of Tennessee, 2506 River Drive, Knoxville, TN 37996-4574, USA
*Corresponding author. E-mail:


Antibiotic resistance (AR) is ancient. Use of antibiotics is a selective driving force that enriches AR genes and promotes the emergence of resistant pathogens. It also has been widely accepted that horizontal gene transfer (HGT) occurs everywhere and plays a critical role in the transmission of AR genes among bacteria. However, our understanding of HGT processes primarily build on extensive in vitro studies; to date, there is still a significant knowledge gap regarding in situ HGT events as well as the factors that influence HGT in different ecological niches. This review is focused on the HGT process in the intestinal tract, a ‘melting pot’ for gene exchange. Several factors that potentially influence in vivo HGT efficiency in the intestine are identified and summarized, which include SOS-inducing agents, stress hormones, microbiota and microbiota-derived factors. We highlight recent discoveries demonstrating that certain antibiotics, which are widely used in animal industry, can enhance HGT in the intestine by serving as DNA-damaging, SOS-inducing agents. Despite recent progress, research on in vivo HGT events is still in its infancy. A better understanding of the factors influencing HGT in the intestine is highly warranted for developing effective strategies to mitigate AR in animal production as well as in future agricultural ecosystems.

Review Article
Copyright © Cambridge University Press 2018 

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Allen, HK, Looft, T, Bayles, DO, Humphrey, S, Levine, UY, Alt, D and Stanton, TB (2011). Antibiotics in feed induce prophages in swine fecal microbiomes. MBio 2: e00260e00211.CrossRefGoogle ScholarPubMed
Alvarez-Martinez, CE and Christie, PJ (2009). Biological diversity of prokaryotic type IV secretion systems. Microbiology and Molecular Biology Reviews 73: 775808.CrossRefGoogle ScholarPubMed
Amita, M, Chowdhury, SR, Thungapathra, M, Ramamurthy, T, Nair, GB and Ghosh, A (2003). Class I integrons and SXT elements in El Tor strains isolated before and after 1992 Vibrio cholerae O139 outbreak, Calcutta, India. Emerging Infectious Diseases 9: 500502.CrossRefGoogle Scholar
Andersson, DI and Hughes, D (2010). Antibiotic resistance and its cost: is it possible to reverse resistance? Nature Reviews: Microbiology 8: 260271.Google ScholarPubMed
Barrett, E, Ross, RP, O'Toole, PW, Fitzgerald, GF and Stanton, C (2012). Gamma-aminobutyric acid production by culturable bacteria from the human intestine. Journal of Applied Microbiology 113: 411417.CrossRefGoogle ScholarPubMed
Beaber, JW, Hochhut, B and Waldor, MK (2004). SOS response promotes horizontal dissemination of antibiotic resistance genes. Nature 427: 7274.CrossRefGoogle ScholarPubMed
Broaders, E, Gahan, CG and Marchesi, JR (2013). Mobile genetic elements of the human gastrointestinal tract: potential for spread of antibiotic resistance genes. Gut Microbes 4: 271280.CrossRefGoogle ScholarPubMed
Burrus, V and Waldor, MK (2004). Shaping bacterial genomes with integrative and conjugative elements. Research in Microbiology 155: 376386.CrossRefGoogle ScholarPubMed
Burrus, V, Pavlovic, G, Decaris, B and Guedon, G (2002). Conjugative transposons: the tip of the iceberg. Molecular Microbiology 46: 601610.CrossRefGoogle ScholarPubMed
Bush, K and Bradford, PA (2016). Beta-lactams and beta-lactamase inhibitors: an overview. Cold Spring Harbor Perspectives in Medicine 6: a025247.CrossRefGoogle ScholarPubMed
Capozzi, V and Spano, G (2009). Horizontal gene transfer in the gut: is it a risk? Food Research International 42: 15011502.CrossRefGoogle Scholar
Charpentier, X, Polard, P and Claverys, JP (2012). Induction of competence for genetic transformation by antibiotics: convergent evolution of stress responses in distant bacterial species lacking SOS? Current Opinion in Microbiology 15: 570576.CrossRefGoogle ScholarPubMed
Christie, PJ and Vogel, JP (2000). Bacterial type IV secretion: conjugation systems adapted to deliver effector molecules to host cells. Trends in Microbiology 8: 354360.CrossRefGoogle ScholarPubMed
Christie, PJ, Atmakuri, K, Krishnamoorthy, V, Jakubowski, S and Cascales, E (2005). Biogenesis, architecture, and function of bacterial type IV secretion systems. Annual Review of Microbiology 59: 451485.CrossRefGoogle ScholarPubMed
Clewell, DB (2007). Properties of Enterococcus faecalis plasmid pAD1, a member of a widely disseminated family of pheromone-responding, conjugative, virulence elements encoding cytolysin. Plasmid 58: 205227.CrossRefGoogle ScholarPubMed
Comeau, AM, Tetart, F, Trojet, SN, Prere, MF and Krisch, HM (2007). Phage-antibiotic synergy (PAS): beta-lactam and quinolone antibiotics stimulate virulent phage growth. PLoS ONE 2: e799.CrossRefGoogle ScholarPubMed
Centers for Disease Control and Prevention (2013). Antibiotic resistance threats in the United States, 2013. Scholar
Crofts, TS, Gasparrini, AJ and Dantas, G (2017). Next-generation approaches to understand and combat the antibiotic resistome. Nature Reviews: Microbiology 15: 422434.Google ScholarPubMed
Cryan, JF and Dinan, TG (2012). Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nature Reviews: Neuroscience 13: 701712.CrossRefGoogle ScholarPubMed
Curtiss, R 3rd (1969). Bacterial conjugation. Annual Review of Microbiology 23: 69136.CrossRefGoogle ScholarPubMed
Davies, J (1996). Origins and evolution of antibiotic resistance. Microbiologia 12: 916.Google ScholarPubMed
Davies, J and Davies, D (2010). Origins and evolution of antibiotic resistance. Microbiology and Molecular Biology Reviews 74: 417433.CrossRefGoogle ScholarPubMed
Dinsdale, EA, Edwards, RA, Hall, D, Angly, F, Breitbart, M, Brulc, JM, Furlan, M, Desnues, C, Haynes, M, Li, L, McDaniel, L, Moran, MA, Nelson, KE, Nilsson, C, Olson, R, Paul, J, Brito, BR, Ruan, Y, Swan, BK, Stevens, R, Valentine, DL, Thurber, RV, Wegley, L, White, BA and Rohwer, F (2008). Functional metagenomic profiling of nine biomes. Nature 452: 629632.CrossRefGoogle ScholarPubMed
Dunny, GM (2007). The peptide pheromone-inducible conjugation system of Enterococcus faecalis plasmid pCF10: cell-cell signalling, gene transfer, complexity and evolution. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 362: 11851193.CrossRefGoogle ScholarPubMed
Dunny, GM (2013). Enterococcal sex pheromones: signaling, social behavior, and evolution. Annual Review of Genetics 47: 457482.CrossRefGoogle ScholarPubMed
Durso, LM, Harhay, GP, Bono, JL and Smith, TP (2011). Virulence-associated and antibiotic resistance genes of microbial populations in cattle feces analyzed using a metagenomic approach. Journal of Microbiological Methods 84: 278282.CrossRefGoogle ScholarPubMed
Erill, I, Campoy, S and Barbe, J (2007). Aeons of distress: an evolutionary perspective on the bacterial SOS response. FEMS Microbiology Reviews 31: 637656.CrossRefGoogle ScholarPubMed
Feld, L, Schjorring, S, Hammer, K, Licht, TR, Danielsen, M, Krogfelt, K and Wilcks, A (2008). Selective pressure affects transfer and establishment of a Lactobacillus plantarum resistance plasmid in the gastrointestinal environment. Journal of Antimicrobial Chemotherapy 61: 845852.CrossRefGoogle ScholarPubMed
Fisher, RA, Gollan, B and Helaine, S (2017). Persistent bacterial infections and persister cells. Nature Reviews: Microbiology 15: 453464.Google ScholarPubMed
Fuqua, WC, Winans, SC and Greenberg, EP (1994). Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators. Journal of Bacteriology 176: 269275.CrossRefGoogle ScholarPubMed
Garcia-Quintanilla, M, Ramos-Morales, F and Casadesus, J (2008). Conjugal transfer of the Salmonella enterica virulence plasmid in the mouse intestine. Journal of Bacteriology 190: 19221927.CrossRefGoogle ScholarPubMed
Ghosh, TS, Gupta, SS, Nair, GB and Mande, SS (2013). In silico analysis of antibiotic resistance genes in the gut microflora of individuals from diverse geographies and age-groups. PLoS ONE 8: e83823.CrossRefGoogle ScholarPubMed
Griffith, F (1928). The significance of pneumococcal types. Journal of Hygiene 27: 113159.CrossRefGoogle ScholarPubMed
Harris, PN, Tambyah, PA and Paterson, DL (2015). Beta-lactam and beta-lactamase inhibitor combinations in the treatment of extended-spectrum beta-lactamase producing Enterobacteriaceae: time for a reappraisal in the era of few antibiotic options? Lancet Infectious Diseases 15: 475485.CrossRefGoogle ScholarPubMed
Havarstein, LS, Coomaraswamy, G and Morrison, DA (1995). An unmodified heptadecapeptide pheromone induces competence for genetic transformation in Streptococcus pneumoniae. Proceedings of the National Academy of Sciences of the United States of America 92: 1114011144.CrossRefGoogle ScholarPubMed
Heaton, MP and Handwerger, S (1995). Conjugative mobilization of a vancomycin resistance plasmid by a putative Enterococcus faecium sex pheromone response plasmid. Microbial Drug Resistance 1: 177183.CrossRefGoogle ScholarPubMed
Hehemann, JH, Correc, G, Barbeyron, T, Helbert, W, Czjzek, M and Michel, G (2010). Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota. Nature 464: 908912.CrossRefGoogle ScholarPubMed
Huddleston, JR (2014). Horizontal gene transfer in the human gastrointestinal tract: potential spread of antibiotic resistance genes. Infection and Drug Resistance 7: 167176.CrossRefGoogle ScholarPubMed
Johnsborg, O, Eldholm, V and Havarstein, LS (2007). Natural genetic transformation: prevalence, mechanisms and function. Research in Microbiology 158: 767778.CrossRefGoogle ScholarPubMed
Johnston, C, Martin, B, Fichant, G, Polard, P and Claverys, JP (2014). Bacterial transformation: distribution, shared mechanisms and divergent control. Nature Reviews: Microbiology 12: 181196.Google ScholarPubMed
Kim, JC, Chui, L, Wang, Y, Shen, J and Jeon, B (2016). Expansion of shiga toxin-producing Escherichia coli by use of bovine antibiotic growth promoters. Emerging Infectious Diseases 22: 802809.CrossRefGoogle ScholarPubMed
Kortman, GA, Raffatellu, M, Swinkels, DW and Tjalsma, H (2014). Nutritional iron turned inside out: intestinal stress from a gut microbial perspective. FEMS Microbiology Reviews 38: 12021234.CrossRefGoogle ScholarPubMed
Lambrecht, E, Bare, J, Chavatte, N, Bert, W, Sabbe, K and Houf, K (2015). Protozoan cysts act as a survival niche and protective shelter for foodborne pathogenic bacteria. Applied and Environmental Microbiology 81: 56045612.CrossRefGoogle ScholarPubMed
Ley, RE, Peterson, DA and Gordon, JI (2006). Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124: 837848.CrossRefGoogle ScholarPubMed
Liu, B and Pop, M (2009). ARDB – antibiotic resistance genes database. Nucleic Acids Research 37: D443D447.CrossRefGoogle ScholarPubMed
Lorenz, MG and Wackernagel, W (1994). Bacterial gene transfer by natural genetic transformation in the environment. Microbiological Reviews 58: 563602.Google ScholarPubMed
Lurie-Weinberger, MN, Peeri, M and Gophna, U (2012). Contribution of lateral gene transfer to the gene repertoire of a gut-adapted methanogen. Genomics 99: 5258.CrossRefGoogle ScholarPubMed
Lyte, M (2011). Probiotics function mechanistically as delivery vehicles for neuroactive compounds: microbial endocrinology in the design and use of probiotics. BioEssays 33: 574581.CrossRefGoogle ScholarPubMed
Marshall, BM and Levy, SB (2011). Food animals and antimicrobials: impacts on human health. Clinical Microbiology Reviews 24: 718733.CrossRefGoogle ScholarPubMed
Matic, I, Rayssiguier, C and Radman, M (1995). Interspecies gene exchange in bacteria: the role of SOS and mismatch repair systems in evolution of species. Cell 80: 507515.CrossRefGoogle ScholarPubMed
McCuddin, ZP, Carlson, SA, Rasmussen, MA and Franklin, SK (2006). Klebsiella to Salmonella gene transfer within rumen protozoa: implications for antibiotic resistance and rumen defaunation. Veterinary Microbiology 114: 275284.CrossRefGoogle ScholarPubMed
Michael, GB, Freitag, C, Wendlandt, S, Eidam, C, Fessler, AT, Lopes, GV, Kadlec, K and Schwarz, S (2015). Emerging issues in antimicrobial resistance of bacteria from food-producing animals. Future Microbiology 10: 427443.CrossRefGoogle ScholarPubMed
Modi, SR, Lee, HH, Spina, CS and Collins, JJ (2013). Antibiotic treatment expands the resistance reservoir and ecological network of the phage metagenome. Nature 499: 219222.CrossRefGoogle ScholarPubMed
Moliner, C, Fournier, PE and Raoult, D (2010). Genome analysis of microorganisms living in amoebae reveals a melting pot of evolution. FEMS Microbiology Reviews 34: 281294.CrossRefGoogle Scholar
Ochman, H, Lawrence, JG and Groisman, EA (2000). Lateral gene transfer and the nature of bacterial innovation. Nature 405: 299304.CrossRefGoogle ScholarPubMed
Olofsson, J, Axelsson-Olsson, D, Brudin, L, Olsen, B and Ellstrom, P (2013). Campylobacter jejuni actively invades the amoeba Acanthamoeba polyphaga and survives within non digestive vacuoles. PLoS ONE 8: e78873.CrossRefGoogle ScholarPubMed
Palmer, BR and Marinus, MG (1994). The dam and dcm strains of Escherichia coli – a review. Gene 143: 112.CrossRefGoogle ScholarPubMed
Pehrsson, EC, Forsberg, KJ, Gibson, MK, Ahmadi, S and Dantas, G (2013). Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs. Frontiers in Microbiology 4: 145.CrossRefGoogle ScholarPubMed
Peterson, G, Kumar, A, Gart, E and Narayanan, S (2011). Catecholamines increase conjugative gene transfer between enteric bacteria. Microbial Pathogenesis 51: 18.CrossRefGoogle ScholarPubMed
Prudhomme, M, Attaiech, L, Sanchez, G, Martin, B and Claverys, JP (2006). Antibiotic stress induces genetic transformability in the human pathogen Streptococcus pneumoniae. Science 313: 8992.CrossRefGoogle ScholarPubMed
Radman, M (1975). SOS repair hypothesis: phenomenology of an inducible DNA repair which is accompanied by mutagenesis. Basic Life Sciences 5A: 355367.Google ScholarPubMed
Salyers, AA, Gupta, A and Wang, Y (2004). Human intestinal bacteria as reservoirs for antibiotic resistance genes. Trends in Microbiology 12: 412416.CrossRefGoogle ScholarPubMed
Schlacher, K and Goodman, MF (2007). Lessons from 50 years of SOS DNA-damage-induced mutagenesis. Nature Reviews: Molecular Cell Biology 8: 587594.CrossRefGoogle ScholarPubMed
Schlundt, J, Saadbye, P, Lohmann, B, Jacobsen, BL and Nielsen, EM (1994). Conjugal transfer of plasmid DNA between Lactococcus lactis strains and distribution of transconjugants in the digestive tract of gnotobiotic rats. Microbial Ecology in Health and Disease 7: 5969.CrossRefGoogle Scholar
Shterzer, N and Mizrahi, I (2015). The animal gut as a melting pot for horizontal gene transfer. Canadian Journal of Microbiology 61: 603605.CrossRefGoogle Scholar
Smith, GR (1991). Conjugational recombination in E. coli: myths and mechanisms. Cell 64: 1927.CrossRefGoogle Scholar
Smith, HO, Danner, DB and Deich, RA (1981). Genetic transformation. Annual Review of Biochemistry 50: 4168.CrossRefGoogle ScholarPubMed
Sommer, MO, Dantas, G and Church, GM (2009). Functional characterization of the antibiotic resistance reservoir in the human microflora. Science 325: 11281131.CrossRefGoogle ScholarPubMed
Sonnenburg, JL (2010). Microbiology: genetic pot luck. Nature 464: 837838.CrossRefGoogle ScholarPubMed
Sun, D, Zhang, Y, Mei, Y, Jiang, H, Xie, Z, Liu, H, Chen, X and Shen, P (2006). Escherichia coli is naturally transformable in a novel transformation system. FEMS Microbiology Letters 265: 249255.CrossRefGoogle Scholar
Szmolka, A and Nagy, B (2013). Multidrug resistant commensal Escherichia coli in animals and its impact for public health. Frontiers in Microbiology 4: 258.CrossRefGoogle ScholarPubMed
Tezcan-Merdol, D, Ljungstrom, M, Winiecka-Krusnell, J, Linder, E, Engstrand, L and Rhen, M (2004). Uptake and replication of Salmonella enterica in Acanthamoeba rhysodes. Applied and Environmental Microbiology 70: 37063714.CrossRefGoogle ScholarPubMed
Tomasz, A (1965). Control of the competent state in Pneumococcus by a hormone-like cell product: an example for a new type of regulatory mechanism in bacteria. Nature 208: 155159.CrossRefGoogle Scholar
Ulrich, RL, Deshazer, D, Kenny, TA, Ulrich, MP, Moravusova, A, Opperman, T, Bavari, S, Bowlin, TL, Moir, DT and Panchal, RG (2013). Characterization of the Burkholderia thailandensis SOS response by using whole-transcriptome shotgun sequencing. Applied and Environmental Microbiology 79: 58305843.CrossRefGoogle ScholarPubMed
Waldor, MK, Tschape, H and Mekalanos, JJ (1996). A new type of conjugative transposon encodes resistance to sulfamethoxazole, trimethoprim, and streptomycin in Vibrio cholerae O139. Journal of Bacteriology 178: 41574165.CrossRefGoogle ScholarPubMed
Waters, CM and Bassler, BL (2005). Quorum sensing: cell-to-cell communication in bacteria. Annual Review of Cell and Developmental Biology 21: 319346.CrossRefGoogle ScholarPubMed
Whitman, WB, Coleman, DC and Wiebe, WJ (1998). Prokaryotes: the unseen majority. Proceedings of the National Academy of Sciences of the USA 95: 65786583.CrossRefGoogle ScholarPubMed
Wise, R (2002). Antimicrobial resistance: priorities for action. Journal of Antimicrobial Chemotherapy 49: 585586.CrossRefGoogle Scholar
Wozniak, RA and Waldor, MK (2010). Integrative and conjugative elements: mosaic mobile genetic elements enabling dynamic lateral gene flow. Nature Reviews: Microbiology 8: 552563.Google ScholarPubMed
Zhu, YG, Johnson, TA, Su, JQ, Qiao, M, Guo, GX, Stedtfeld, RD, Hashsham, SA and Tiedje, JM (2013). Diverse and abundant antibiotic resistance genes in Chinese swine farms. Proceedings of the National Academy of Sciences of the USA 110: 34353440.CrossRefGoogle ScholarPubMed
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