Inducible Expression of both ermB and ermT Conferred High Macrolide Resistance in Streptococcus gallolyticus subsp. pasteurianus Isolates in China.
Streptococcus gallolyticus subsp. pasteurianus is an under-recognized pathogen and zoonotic agent causing opportunistic infections in humans. Despite increasing recognition of this subspecies as a cause for human infectious diseases, limited information is known about its antibiotic resistance mechanism. In this study, we aim to identify the molecular mechanism underlying the high macrolide resistance of six S. gallolyticus subsp. pasteurianus isolates from dead ducklings collected in several natural outbreaks in China during 2010-2013. All isolates exhibited multi-drug resistance including high macrolide resistance (MIC ≥ 1024 mg/L for erythromycin, and 512 mg/L for clarithromycin). Efflux-encoding mefA and mefE genes were not detectable in these isolates. The presence of 23S rRNA mutations in specific isolates did not significantly change macrolide MICs. No nucleotide substitutions were found in genes encoding ribosomal proteins L4 or L22. The ermB and ermT genes were found in the genomes of all isolates. These two genes were acquired independently in one highly virulent isolate AL101002, and clustered with Tn916 and IS1216, respectively. The expression of both ermB and ermT in all isolates was erythromycin inducible and yielded comparable macrolide MICs in all six isolates. Taken together, inducible expression of both ermB and ermT conferred high macrolide resistance in these S. gallolyticus subsp. pasterianus isolates. Our findings reveal new macrolide resistance features in S. gallolyticus subsp. pasteurianus by both ermB and ermT.
College of Veterinary Medicine, Huazhong Agricultural University, 1st Shizishan Street, Wuhan 430070, China. mislimeixia@126.com.
Meixia
M
Li
College of Veterinary Medicine, Huazhong Agricultural University, 1st Shizishan Street, Wuhan 430070, China. cccaochao@yeah.net.
Chao
C
Cai
College of Veterinary Medicine, Huazhong Agricultural University, 1st Shizishan Street, Wuhan 430070, China. cj879503625@163.com.
Juan
J
Chen
College of Veterinary Medicine, Huazhong Agricultural University, 1st Shizishan Street, Wuhan 430070, China. 13027120595@163.com.
Changwei
C
Cheng
College of Veterinary Medicine, Huazhong Agricultural University, 1st Shizishan Street, Wuhan 430070, China. chengguofu@mail.hzau.edu.cn.
Guofu
G
Cheng
College of Veterinary Medicine, Huazhong Agricultural University, 1st Shizishan Street, Wuhan 430070, China. hxying@mail.hzau.edu.cn.
Xueying
X
Hu
College of Veterinary Medicine, Huazhong Agricultural University, 1st Shizishan Street, Wuhan 430070, China. Cuiping.Liu@mail.hzau.edu.cn.
Cuiping
C
Liu
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D002681:China; D017291:Clarithromycin / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D004917:Erythromycin / Q000494:pharmacology; D018942:Macrolides / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics; D008826:Microbial Sensitivity Tests; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D000070099:Streptococcus gallolyticus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D014774:Virulence / Q000235:genetics
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D018942:Macrolides; C117866:MefA protein, Streptococcus; D008565:Membrane Proteins; D012338:RNA, Ribosomal, 23S; D004917:Erythromycin; D017291:Clarithromycin
Streptococcus gallolyticus subsp. pasteurianus; ermB; ermT; macrolide
Antimicrob Agents Chemother. 2002 Sep;46(9):3054-6
12183270
Curr Infect Dis Rep. 2016 Mar;18(4):11
26879740
Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18261-6
19015512
Clin Infect Dis. 2002 Feb 15;34(4):482-92
11797175
Avian Pathol. 2002 Aug;31(4):393-7
12396341
J Med Microbiol. 2003 Oct;52(Pt 10):903-8
12972586
Pediatr Int. 2014 Apr;56(2):282-5
24730635
Int J Syst Evol Microbiol. 2002 Jul;52(Pt 4):1247-55
12148636
Eur J Clin Microbiol Infect Dis. 2013 Sep;32(9):1171-6
23558362
Clin Microbiol Infect. 2015 Dec;21(12):1077-83
26314916
J Infect Chemother. 2012 Apr;18(2):265-8
22002578
J Clin Microbiol. 2012 Jan;50(1):57-60
22075594
Avian Dis. 2014 Jun;58(2):318-22
25055641
Transfusion. 2013 Oct;53(10):2207-10
23347218
Vet J. 2008 May;176(2):251-3
17412621
Proc Natl Acad Sci U S A. 1980 Dec;77(12):7079-83
6938954
Infection. 2013 Apr;41(2):329-37
22886774
Korean J Pediatr. 2015 Jan;58(1):33-6
25729397
Clin Microbiol Infect. 2014 May;20(5):405-9
24033711
J Infect. 2014 Aug;69(2):145-53
24637236
Pediatr Infect Dis J. 2016 Nov;35(11):1272-1275
27355933
Diagn Microbiol Infect Dis. 2016 Jun;85(2):239-42
27117515
Antimicrob Agents Chemother. 2005 Nov;49(11):4635-40
16251306
Antimicrob Agents Chemother. 1995 Apr;39(4):797-805
7785974
Antimicrob Agents Chemother. 2001 Dec;45(12):3362-5
11709309
Mol Microbiol. 2007 Nov;66(4):1039-50
17956547
Int J Infect Dis. 2007 Jul;11(4):329-36
17320446
Jpn J Infect Dis. 2015;68(3):251-3
25866113
J Clin Microbiol. 2013 Dec;51(12):4249-51
24025909
Nat Commun. 2014 Mar 24;5:3501
24662426
Vet Microbiol. 2013 Mar 23;162(2-4):930-6
23294860
Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17152-7
20876128
Microb Drug Resist. 2015 Apr;21(2):121-9
25115711
Microbiology. 2016 Jan;162(1):46-52
26531240
J Antimicrob Chemother. 1999 Apr;43(4):559-62
10350387
BMC Infect Dis. 2012 Nov 23;12:320
23176582
J Clin Microbiol. 1990 Sep;28(9):1942-6
2095137
BMJ Case Rep. 2014 May 05;2014:null
24798358
J Biol Chem. 1983 Oct 25;258(20):12702-6
6195156
Antimicrob Agents Chemother. 2005 Oct;49(10):4347-50
16189118
J Clin Microbiol. 2010 Jun;48(6):2247-9
20357211
Antimicrob Agents Chemother. 2005 Apr;49(4):1646-8
15793162
Eur J Clin Microbiol Infect Dis. 2015 Apr;34(4):719-25
25416160
Diagn Microbiol Infect Dis. 2007 Feb;57(2):189-93
16989973
Int J Syst Evol Microbiol. 2003 May;53(Pt 3):631-45
12807180
Enferm Infecc Microbiol Clin. 2016 Feb;34(2):141-2
26183441
Microb Drug Resist. 2003;9 Suppl 1:S35-8
14633365
Microbiol Rev. 1996 Jun;60(2):366-85
8801438