Abstract
Antimicrobial resistance makes pathogenic bacteria hard to control, but little is known about the general processes of resistance gain or loss. Here, we compared distinct S. typhimurium DT104 strains resistant to zero, two, five, or more of the tested antimicrobials. We found that common resistance phenotypes could be encoded by distinct genes, on SGI-1 or plasmid. We also demonstrated close clonality among all the tested non-resistant and differently resistant DT104 strains, demonstrating dynamic acquisition or loss (by total deletion or gradual decaying of multi-drug resistance gene clusters) of the genetic traits. These findings reflect convergent processes to make the bacteria resistant to multiple antimicrobials by acquiring the needed traits from stochastically available origins. When the antimicrobial stress is absent, the resistance genes may be dropped off quickly, so the bacteria can save the cost for maintaining unneeded genes. Therefore, this work reiterates the importance of strictly controlled use of antimicrobials.
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References
Bao HX, Tang L, Yu L, Wang XY, Li Y, Deng X, Li YG, Li A, Zhu DL, Johnston RN, Liu GR, Feng Y, Liu SL (2014) Differential efficiency in exogenous DNA acquisition among closely related Salmonella strains: implications in bacterial speciation. BMC Microbiol 14:157
Bochner BR, Huang HC, Schieven GL, Ames BN (1980) Positive selection for loss of tetracycline resistance. J Bacteriol 143:926–933
Boyd D, Peters GA, Cloeckaert A, Boumedine KS, Chaslus-Dancla E, Imberechts H, Mulvey MR (2001) Complete nucleotide sequence of a 43-kilobase genomic island associated with the multidrug resistance region of Salmonella enterica serovar Typhimurium DT104 and its identification in phage type DT120 and serovar Agona. J Bacteriol 183:5725–5732
Chen F, Liu WQ, Eisenstark A, Johnston RN, Liu GR, Liu SL (2010a) Multiple genetic switches spontaneously modulating bacterial mutability. BMC Evol Biol 10:277
Chen F, Liu WQ, Liu ZH, Zou QH, Wang Y, Li YG, Zhou J, Eisenstark A, Johnston RN, Liu GR, Yang BF, Liu SL (2010b) mutL as a genetic switch of bacterial mutability: turned on or off through repeat copy number changes. FEMS Microbiol Lett 312:126–132
Cooke FJ, Brown DJ, Fookes M, Pickard D, Ivens A, Wain J, Roberts M, Kingsley RA, Thomson NR, Dougan G (2008) Characterization of the genomes of a diverse collection of Salmonella enterica serovar Typhimurium definitive phage type 104. J Bacteriol 190:8155–8162
Fekete PZ, Nagy B (2008) Salmonella Genomic Island 1 (SGI1) and genetic characteristics of animal and food isolates of Salmonella typhimurium DT104 in Hungary. Acta Vet Hung 56:5–11
Gong J, Liu WQ, Liu GR, Chen F, Li JQ, Xu GM, Wang L, Johnston RN, Eisenstark A, Liu SL (2007) Spontaneous conversion between mutL and 6 bpDeltamutL in Salmonella typhimurium LT7: association with genome diversification and possible roles in bacterial adaptation. Genomics 90:542–549
Hermans AP, Beuling AM, van Hoek AH, Aarts HJ, Abee T, Zwietering MH (2006) Distribution of prophages and SGI-1 antibiotic-resistance genes among different Salmonella enterica serovar Typhimurium isolates. Microbiology 152:2137–2147
Kothapalli S, Nair S, Alokam S, Pang T, Khakhria R, Woodward D, Johnson W, Stocker BA, Sanderson KE, Liu SL (2005) Diversity of Genome Structure in Salmonella enterica Serovar Typhi Populations. J Bacteriol 187:2638–2650
Liu SL (2007) Physical mapping of Salmonella genomes. Methods Mol Biol 5:39–58
Liu SL, Sanderson KE (1992) A physical map of the Salmonella typhimurium LT2 genome made by using XbaI analysis. J Bacteriol 174:1662–1672
Liu SL, Sanderson KE (1995) Rearrangements in the genome of the bacterium Salmonella typhi. Proc Natl Acad Sci USA 92:1018–1022
Liu SL, Sanderson KE (1996) Highly plastic chromosomal organization in Salmonella typhi. Proc Natl Acad Sci USA 93:10303–10308
Liu SL, Hessel A, Sanderson KE (1993) The XbaI-BlnI-CeuI genomic cleavage map of Salmonella typhimurium LT2 determined by double digestion, end labelling, and pulsed-field gel electrophoresis. J Bacteriol 175:4104–4120
Liu GR, Rahn A, Liu WQ, Sanderson KE, Johnston RN, Liu SL (2002) The evolving genome of Salmonella enterica serovar Pullorum. J Bacteriol 184:2626–2633
Liu GR, Liu WQ, Johnston RN, Sanderson KE, Li SX, Liu SL (2006) Genome plasticity and ori-ter rebalancing in Salmonella typhi. Mol Biol Evol 23:365–371
Mather AE, Reid SW, Maskell DJ, Parkhill J, Fookes MC, Harris SR, Brown DJ, Coia JE, Mulvey MR, Gilmour MW, Petrovska L, de Pinna E, Kuroda M, Akiba M, Izumiya H, Connor TR, Suchard MA, Lemey P, Mellor DJ, Haydon DT, Thomson NR (2013) Distinguishable epidemics of multidrug-resistant Salmonella Typhimurium DT104 in different hosts. Science 341:1514–1517
Mulvey MR, Boyd DA, Olson AB, Doublet B, Cloeckaert A (2006) The genetics of Salmonella genomic island 1. Microbes Infect 5:56
Parkhill J, Dougan G, James KD, Thomson NR, Pickard D, Wain J, Churcher C, Mungall KL, Bentley SD, Holden MT, Sebaihia M, Baker S, Basham D, Brooks K, Chillingworth T, Connerton P, Cronin A, Davis P, Davies RM, Dowd L, White N, Farrar J, Feltwell T, Hamlin N, Haque A, Hien TT, Holroyd S, Jagels K, Krogh A, Larsen TS, Leather S, Moule S, O’Gaora P, Parry C, Quail M, Rutherford K, Simmonds M, Skelton J, Stevens K, Whitehead S, Barrell BG (2001) Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18. Nature 413:848–852
Pillon MC, Dubinsky M, Johnston RN, Liu SL, Guarne A (2013) Characterization of the defects in the ATP lid of E. coli MutL that cause transient hypermutability. DNA Repair 12:864–869
Poppe C, Ziebell K, Martin L, Allen K (2002) Diversity in antimicrobial resistance and other characteristics among Salmonella typhimurium DT104 isolates. Microb Drug Resist 8:107–122
Song J, Ware A, Liu SL (2003) Wavelet to predict bacterial ori and ter: a tendency towards a physical balance. BMC Genom 4:17
Tang L, Liu SL (2012) The 3Cs provide a novel concept of bacterial species: messages from the genome as illustrated by Salmonella. Antonie Van Leeuwenhoek 101:67–72
Tang L, Li Y, Deng X, Johnston RN, Liu GR, Liu SL (2013a) Defining natural species of bacteria: clear-cut genomic boundaries revealed by a turning point in nucleotide sequence divergence. BMC Genom 14:489
Tang L, Wang CX, Zhu SL, Li Y, Deng X, Johnston RN, Liu GR, Liu SL (2013b) Genetic boundaries to delineate the typhoid agent and other Salmonella serotypes into distinct natural lineages. Genomics 102:331–337
Threlfall EJ, Frost JA, Ward LR, Rowe B (1994) Epidemic in cattle and humans of Salmonella typhimurium DT 104 with chromosomally integrated multiple drug resistance. Vet Rec 134:577
Wu KY, Liu GR, Liu WQ, Wang AQ, Zhan S, Sanderson KE, Johnston RN, Liu SL (2005) The genome of Salmonella enterica serovar gallinarum: distinct insertions/deletions and rare rearrangements. J Bacteriol 187:4720–4727
Zhao EY, Bao HX, Tang L, Zou QH, Liu WQ, Zhu DL, Chin J, Dong YY, Li YG, Cao FL, Poppe C, Sanderson KE, Johnston RN, Zhou D, Liu GR, Liu SL (2013) Genomic comparison of Salmonella typhimurium DT104 with non-DT104 strains. Mol Genet Genomics 288:549–557
Funding
This study was funded by a grant of the National Natural Science Foundation of China (NSFC31600001), a National Postdoctoral Fellowship of China (2016M600266), and an Alberta Innovates Health Solutions (AIHS) Postdoctoral Fellowship of Canada to LT; Genome Canada grant 256177 to CP; and grants of the National Science Foundation of China (NSFC81030029, 81271786, 81671980, and 81871623) to SLL.
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Tang, L., Zhu, SL., Fang, X. et al. Distinct evolutionary origins of common multi-drug resistance phenotypes in Salmonella typhimurium DT104: a convergent process for adaptation under stress. Mol Genet Genomics 294, 597–605 (2019). https://doi.org/10.1007/s00438-019-01531-5
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DOI: https://doi.org/10.1007/s00438-019-01531-5