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PLOS ONE logoLink to PLOS ONE
. 2017 May 1;12(5):e0176695. doi: 10.1371/journal.pone.0176695

Database for the ampC alleles in Acinetobacter baumannii

Nabil Karah 1,2,*, Keith A Jolley 3, Ruth M Hall 4, Bernt Eric Uhlin 1,2
Editor: Feng Gao5
PMCID: PMC5411055  PMID: 28459877

Abstract

Acinetobacter baumannii is a troublesome opportunistic pathogen with a high capacity for clonal dissemination. We announce the establishment of a database for the ampC locus in A. baumannii, in which novel ampC alleles are differentiated based on the occurrence of ≥ 1 nucleotide change, regardless of whether it is silent or missense. The database is openly accessible at the pubmlst platform for A. baumannii (http://pubmlst.org/abaumannii/). Forty-eight distinctive alleles of the ampC locus have so far been identified and deposited in the database. Isolates from clonal complex 1 (CC1), according to the Pasteur multilocus sequence typing scheme, had a variety of the ampC locus alleles, including alleles 1, 3, 4, 5, 6, 7, 8, 13, 14, 17, and 18. On the other hand, isolates from CC2 had the ampC alleles 2, 3, 19, 20, 21, 22, 23, 24, 26, 27, 28, and 46. Allele 3 was characteristic for sequence types ST3 or ST32. The ampC alleles 10, 16, and 25 were characteristic for CC10, ST16, and CC25, respectively. Our study points out that novel gene databases, in which alleles are numbered based on differences in their nucleotide identities, should replace traditional records that use amino acid substitutions to define new alleles.

Introduction

Acinetobacter baumannii is a clinically important pathogen responsible for a wide range of hospital-acquired infections [1]. The ampC gene of A. baumannii was cloned and sequenced for the first time in 2000 [2]. The gene, also called blaADC for Acinetobacter-Derived Cephalosporinase, is intrinsic in A. baumannii and all other members of the Acinetobacter calcoaceticus-Acinetobacter baumannii (Acb) complex [3, 4]. It is located in the chromosome between folE, encoding a GTP cyclohydrolase I enzyme, and an open reading frame encoding a hypothetical protein, as seen in the A. baumannii reference strain ATCC 17978-mff (GenBank accession number CP012004, locus tag ACX60_05710). Overexpression of ampC, due to the acquisition of a strong promoter located on an insertion sequence (IS) element, is the main mechanism of resistance to third-generation cephalosporins in A. baumannii [5]. With few exceptions, variation in the amino acid sequence of AmpC in A. baumannii usually does not affect the resistance spectrum [6, 7].

Some A. baumannii isolates were reported to carry a second copy of the ampC gene, located elsewhere in the chromosome [8, 9]. The additional copy was part of a DNA segment most likely derived from the chromosome of another A. baumannii strain. The segment was mobilized as part of Tn6168, a composite transposon made of two directly oriented copies of ISAba1 [8]. The A. baumannii ampC gene, together with an upstream ISOur1, was also detected in the genome of Oligella urethralis, leading to a cephalosporin resistance phenotype [10]. Interestingly, A. baumannii strain ACICU, from global clone 2 (GC2), was found to carry a 9 kb chromosomal segment, containing ISAba125-ampC, which was derived from a GC1 isolate [11]. This finding indicated the occurrence of a replacement in the chromosome of ACICU, most likely mediated by a homologous recombination event [11]. Similarly, distinctive ISAba1-associated ampC alleles were detected in the genome of GC1 isolates, once again highlighting the frequent occurrence of horizontal transfer of chromosomal DNA segments in A. baumannii [9, 12].

To track these imports, a clear numbering system of the ampC alleles is needed. Analysis of the ampC locus could also be a convenient method for exploring the molecular epidemiology of A. baumannii, taking into consideration that particular ampC alleles have been linked to certain clones of A. baumannii [9, 13]. This report aims to announce the establishment of a database for the ampC locus in A. baumannii.

New database for the ampC locus in A. baumannii

The database is hosted and maintained at the pubmlst platform for A. baumannii (http://pubmlst.org/abaumannii/) sited at the University of Oxford [14]. The platform provides an open access to all the data and allows submissions of novel sequences. However, novel sequence must simultaneously be submitted and assigned accession numbers by the International Nucleotide Sequence Database Collaboration (INSDC) (http://www.insdc.org/). Sequences must be complete and meet the validation criteria of INSDC. ampC sequences with novel nucleotide identities (≥ 1 nucleotide substitution) will be numbered successively.

So far, we have identified, curated and numbered a total of 48 distinctive alleles of the ampC locus in a collection of 188 A. baumannii isolates by means of the online available whole genome sequence records (Table 1). The ampC alleles 1, 3, 4, 5, 6, 7, 8, 13, 14, 17, and 18 were carried by isolates that belong to clonal complex 1 (CC1), corresponding to GC1, according to the Pasteur scheme for multilocus sequence typing (https://pubmlst.org/abaumannii/). Isolates from CC2, corresponding to GC2, had the ampC alleles 2, 3, 19, 20, 21, 22, 23, 24, 26, 27, 28, and 46. Nonetheless, ampC allele 2 was also present in one isolate from ST215 (27, 2, 7, 2, 2, 1, 2), which was not closely related to CC2. Similarly, allele 19 was present in isolates of ST500 (3, 3, 2, 2, 28, 1, 5) or ST522 (3, 3, 89, 2, 28, 1, 5), which were also not related to CC2. Although it was present in few isolates from CC1 and CC2, allele 3 was mainly characteristic for ST3 (3, 3, 2, 2, 3, 1, 3) or ST32 (1, 1, 2, 2, 3, 4, 4). The ampC locus alleles 10 and 16 were characteristic for CC10 and ST16, respectively. Likewise, all isolates from CC25 had the ampC locus allele 25. Allele 39 was present in all the ST78 (25, 3, 6, 2, 28, 1, 29) isolates, but also in one isolate from ST241 (40, 3, 15, 2, 40, 4, 4).

Table 1. Numeration of the ampC gene alleles in Acinetobacter baumannii.

ampC allele Isolate Pasteur scheme multi locus sequence type GenBank accession PubMed IDentifier (PMID) / GenBank submission authors / other references
1 AYE ST1 (1, 1, 1, 1, 5, 1, 1) NC_010410 16415984; [9]
AB5075 ST1 CP008706; AHAH00000000 24865555; [9]
A1 ST1 CP010781 25767221; [9]
3208 ST1 FJ172370.5; FBWZ00000000 19364869; [9]
D2 ST1 GQ406245.5; FBWY00000000 20375036; [9]
A92 ST1 GQ406246.3; FBWV00000000 20375036; [9]
A85 (intrinsic) ST1 KC118540.6; FBXA00000000 24907141; [9]
AB307-0294 ST1 CP001172 18931120; [9]
AB0057 (intrinsic) ST1 CP001182 18931120; [9]
6772166 (intrinsic) ST1 FBWX00000000 [9]
RBH3 (intrinsic) ST1 FBXD00000000 [9]
AB056 (intrinsic) ST1 ADGZ00000000 20530228; [9]
AB059 (intrinsic) ST1 ADHB00000000 20530228; [9]
AB_908–13 (intrinsic) ST1 AMHW00000000 23365658; [9]
AB_909-02-7 (intrinsic) ST1 AMHZ00000000 23365658; [9]
TG19582 ST1 AMIV00000000 23365658; [9]
Canada BC-1 (intrinsic) ST1 AMSZ00000000 Harkins et al., unpublished; [9]
Canada BC-5 (intrinsic) ST1 AFDN00000000 Harkins et al., unpublished; [9]
IS-58 ST1 AMGH00000000 Harkins et al., unpublished; [9]
IS-235 ST1 AMEI00000000 Harkins et al., unpublished
IS-251 ST1 AMEJ00000000 Harkins et al., unpublished
NIPH 290 ST1 APRD00000000 Feldgarden et al., unpublished; [9]
NIPH 527 (RUH875) ST1 APQW00000000 Cerqueira et al., unpublished; [9]
ANC 4097 ST1 APRF00000000 Cerqueira et al., unpublished; [9]
Naval-83 ST20 (3, 1, 1, 1, 5, 1, 1) AMFK00000000 Harkins et al., unpublished; [9]
2 A91 ST2 (2, 2, 2, 2, 2, 2, 2) JN968483 22351684
NIPH 2061 ST2 APOW00000000 24277043
OIFC180 ST2 AMDQ00000000 Harkins et al., unpublished
CI77 ST2 AVOC00000000 24503987
MRY09-0642 ST2 BASA00000000 23868126
ORAB01 ST2 CP015483 Adams et al., unpublished
XH856 ST2 CP014541 Feng et al., unpublished
YU-R612 ST2 CP014215 27139604
XH386 ST2 CP010779 26981403
NCGM 237 ST2 AP013357 24550340
BJAB0868 ST2 CP003849 23826102
BJAB07104 ST2 CP003846 23826102
MDR-ZJ06 ST2 CP001937 21788470
TCDC-AB0715 ST2 CP002522.2 21398540
ABNIH2 ST2 AFTA00000000 21825119
AB210 ST2 AEOX00000000 21565804
Naval-17 ST2 AFDO00000000 Harkins et al., unpublished
Ab11111 ST2 AKAQ00000000 Murphy et al., unpublished
ZWS1122 ST2 AMGR00000000 23209232
ZWS1219 ST2 AMGS00000000 23209232
Naval-113 ST2 AMZU00000000 Harkins et al., unpublished
XH857 ST215 (27, 2, 7, 2, 2, 1, 2) CP014540 Feng et al., unpublished
3 A085 ST3 (3, 3, 2, 2, 3, 1, 3) KP881239 26824943
AB4456 ST3 LREF00000000 Arivett et al., unpublished
AB3560 ST3 LRDV00000000 Arivett et al., unpublished
AB4857 ST3 AHAG00000000 22374953
OIFC137 ST3 AFDK00000000 Harkins et al., unpublished
OIFC109 ST3 ALAL00000000 Harkins et al., unpublished
IS-123 ST3 ALII00000000 Harkins et al., unpublished
Naval-81 ST3 AFDB00000000 Harkins et al., unpublished
Naval-13 ST3 AMDR00000000 Harkins et al., unpublished
WC-A-694 ST3 AMTA00000000 Harkins et al., unpublished
OIFC032 ST32 (1, 1, 2, 2, 3, 4, 4) AFCZ00000000 Harkins et al., unpublished
OIFC087 ST32 AMFS00000000 Harkins et al., unpublished
OIFC099 ST32 AMFT00000000 Harkins et al., unpublished
1525283 ST32 JEXR00000000 Harris et al., unpublished
781407 ST32 JEZS00000000 Harris et al., unpublished
ABBL013 ST32 LLCT00000000 26699703
OIFC074 ST19 (1, 2, 1, 1, 5, 1, 1) AMDE00000000 Harkins et al., unpublished; [9]
Naval-21 ST19 AMSY00000000 Harkins et al., unpublished; [9]
1999BJAB11 ST2 JSDB00000000 25487793
IS-143 ST414 (2, 2, 2, 2, 2, 37, 2) AMGE00000000 Harkins et al., unpublished
4 D15 ST1 FBXJ00000000 [9]
D13 ST1 FBXI00000000 [9]
5 G7 ST1 FBXF00000000 [9]
6 AB058 ST20 ADHA00000000 20530228; [9]
7a A388 ST1 JQ684178; FBXE00000000 22915466; [9]
A100 ST1 KP881241 26824943
8a A85 (acquired) ST1 KC118540.6; FBXA00000000 24907141
AB0057 (acquired) ST1 CP001182 18931120; [9]
6772166 (acquired) ST1 FBWX00000000 [9]
RBH3 (acquired) ST1 FBXD00000000 [9]
AB056 (acquired) ST1 ADGZ00000000 20530228; [9]
AB059 (acquired) ST1 ADHB00000000 20530228; [9]
AB_908–13 (acquired) ST1 AMHW00000000 23365658; [9]
AB_909-02-7 (acquired) ST1 AMHZ00000000 23365658; [9]
Canada BC-1 (acquired) ST1 AMSZ00000000 Harkins et al., unpublished; [9]
Canada BC-5 (acquired) ST1 AFDN00000000 Harkins et al., unpublished; [9]
9 NIPH 190 ST9 (3, 1, 5, 3, 6, 1, 3) APPL00000000 24277043
10 T214 ST10 (1, 3, 2, 1, 4, 4, 4) JRTZ00000000 Kamolvit et al., unpublished
NIPH 335 ST10 APQX00000000 Cerqueira et al., unpublished
OIFC098 ST10 AMDF00000000 Harkins et al., unpublished
466760 ST10 JEXB00000000 Harris et al., unpublished
50595 ST10 JEXP00000000 Harris et al., unpublished
3390 ST10 JFER00000000 Harris et al., unpublished
1262761–105 ST10 JMOJ00000000 Harris et al., unpublished
Ab04-mff ST10 CP012006 26170289
A078 ST23 (1, 3, 10, 1, 4, 4, 4) KP881236 26824943
BJAB0715 ST23 CP003847 23826102
XH858 ST23 CP014528 Feng et al., unpublished
11 NIPH 329 ST11 (1, 2, 6, 2, 3, 4, 4) APQY00000000 24277043
12 NIPH 615 ST12 (3, 5, 7, 1, 7, 2, 6) APOV00000000 24277043
13 A076 ST1 KP881235 26824943
14 A082 ST1 KP881238 26824943
15b NIPH 1734 (LUH 8406) ST15 (6, 6, 8, 2, 3, 5, 4) APOX00000000 24277043
16 UMB002 ST16 (7, 7, 2, 2, 8, 4, 4) AEPL00000000 21639920
1043794 ST16 JEYX00000000 Harris et al., unpublished
972082 ST16 JFAA00000000 Harris et al., unpublished
232184 ST16 JEYI00000000 Harris et al., unpublished
268680 ST16 JEYN00000000 Harris et al., unpublished
655378 ST16 JFCE00000000.2 Harris et al., unpublished
1064293_45 ST16 JFDS00000000 Harris et al., unpublished
17c D36 ST81 (1, 1, 1, 1, 5, 1, 2) CP012952 26679588; [9]
18c D81 ST1 FBXC00000000 [9]
D78 ST1 FBXH00000000 [9]
19c RUH 134 (A320) ST2 JN247441 23788477
NIPH 24 ST2 APOF00000000 Cerqueira et al., unpublished
NIPH 528 ST2 APRB00000000 Cerqueira et al., unpublished
OIFC338 ST2 AMFX00000000 Harkins et al., unpublished
XH859 ST2 CP014539 Feng et al., unpublished
AB1H8 ST2 ANNC00000000 23723398
AB5711 ST2 AHAJ00000000 22374953
472237–120 ST500 (3, 3, 2, 2, 28, 1, 5) JFCW00000000 Harris et al., unpublished
1188188 ST500 JFDV00000000 Harris et al., unpublished
1271213 ST500 JFDX00000000 Harris et al., unpublished
1237893 ST500 JFEA00000000 Harris et al., unpublished
480175 ST500 JFEU00000000 Harris et al., unpublished
1276470–86 ST500 JFXE00000000 Harris et al., unpublished
1121032 ST500 JEZE00000000.2 Harris et al., unpublished
940793 ST500 JMNW00000000 Harris et al., unpublished
29280 ST522 (3, 3, 89, 2, 28, 1, 5) JEZI00000000 Harris et al., unpublished
20 A072 ST2 KP881233 26824943
XH860 ST2 CP014538 Feng et al., unpublished
AC29 ST2 CP007535 26824943
AC30 ST2 CP007577 26824943
PKAB07 ST2 CP006963 24652977
21 J65 ST2 JQ867374 Wang, unpublished
22d MDR_MMC4 ST2 AZNQ00000000 20609238
23 1656–2 ST2 CP001921 22038960
DU202 ST2 AVGF00000000 24486871
24 TYTH-1 ST2 CP003856 23209228
KBN10P02143 ST2 CP013924 27143492
25 OIFC143 ST25 (3, 3, 2, 4, 7, 2, 4) AFDL00000000 Harkins et al., unpublished
Naval-18 ST25 AFDA00000000 Harkins et al., unpublished
NIPH 146 ST25 APOU00000000 Cerqueira et al., unpublished
CI86 ST25 AVOB00000000 24503987
CI79 ST25 AVOD00000000 24503987
984213 ST25 JEVX00000000 Harris et al., unpublished
1429530 ST25 JEWM00000000 Harris et al., unpublished
NM3 ST25 JZBV00000000 23264451
RUH 1486 ST25 JZBU00000000 26462752
LUH 6220 ST25 JZBW00000000 26462752
161/07 ST25 JZCA00000000 26462752
4390 ST25 JZBY00000000 26462752
LUH 7841 ST402 (3, 3, 2, 1, 7, 2, 4) JZBX00000000 26462752
26 58452 ST2 JEZV00000000 Harris et al., unpublished
27 UH10007 ST2 AYGO00000000 24449752
28d Naval-2 ST2 AMSX00000000 Harkins et al., unpublished
TG15234 ST2 ASEW00000000 23365658
TG15240 ST2 ASFB00000000 23365658
1043903 ST2 JEYY00000000 Harris et al., unpublished
17534 ST2 JEYQ00000000 Harris et al., unpublished
1294217 ST2 JEWF01000000 Harris et al., unpublished
1406750 ST2 JEWK00000000 Harris et al., unpublished
724909 ST2 JEXF01000000 Harris et al., unpublished
UMB001 ST2 AEPK00000000 21639920
ABIsac_ColiS ST2 CAKA00000000 23070160
29 NIPH 1669 ST3 APOQ00000000 24277043
30e LAC-4 ST10 JICJ00000000 Cerqueira et al., unpublished
31 D46 ST25 KF030679.2 23788477
32 NIPH 60 ST34 (8, 1, 14, 3, 12, 1, 13) APPM00000000 24277043
33 NIPH 67 ST35 (9, 3, 2, 2, 5, 4, 14) APRA00000000 24277043
34 NIPH 80 ST37 (3, 2, 2, 2, 7, 1, 2) APRE00000000 24277043
35 NIPH 201 ST38 (3, 2, 15, 6, 6, 4, 5) APQV00000000 24277043
36 NIPH 601 ST40 (1, 2, 2, 2, 5, 1, 14) APQZ00000000 24277043
37 J9 ST49 (3, 3, 6, 2, 3, 1, 5) KF002790 23920428
38 ATCC 19606 ST52 (3, 2, 2, 7, 9, 1, 5) APRG00000000 24277043
39 UH5207 ST78 (25, 3, 6, 2, 28, 1, 29) AYFP00000000 24449752
1096934 ST78 JEXM00000000 Harris et al., unpublished
831240 ST78 JEYO00000000 Harris et al., unpublished
855125 ST78 JMNT00000000 Harris et al., unpublished
118362 ST241 (40, 3, 15, 2, 40, 4, 4) JEWB00000000 Harris et al., unpublished
40 A099 ST85 (5, 2, 4, 1, 3, 3, 4) KP881240 26824943
41 RBH2 ST111 (3, 3, 2, 2, 4, 8, 12) KF030678 23788477
42 CIP 70.10 ST126 (3, 2, 7, 2, 7, 1, 3) LN865143 Wibberg et al., unpublished
233846 ST126 JMOG00000000 Harris et al., unpublished
1419130 ST529 (3, 3, 7, 52, 7, 1, 4) JEWL00000000 Harris et al., unpublished
43 AA-014 ST158 (41, 42, 13, 1, 5, 4, 14) AMGA00000000 Harkins et al., unpublished
44 AB4A3 ST255 (3, 37, 2, 2, 42, 1, 14) AOLU00000000 23723398
45 AB_TG2030 ST406 (1, 1, 1, 2, 65, 1, 5) AMIJ00000000 Sahl et al., unpublished
46 16553_10 ST415 (2, 2, 2, 2, 68, 2, 2) JHPF0000000 Harris et al., unpublished
47 1406589 ST521 (3, 88, 2, 2, 28, 1, 5) JFYI00000000 Harris et al., unpublished
48 A074 ST636 (2, 1, 2, 2, 2, 1, 1) KP881234 26824943

a Indicates extra 15 nucleotides in the DNA sequence of alleles 7 and 8, which were previously designated as alleles 1 and 3, respectively [9]; The two alleles have different extra nucleotides.

b Allele 15 was also detected in the genome of Oligella urethralis [2]

c Alleles 17, 18, and 19 were previously designated as 1a,1b, and 2, respectively [9]

d Indicates extra 3 nucleotides in the DNA sequence of alleles 22 and 28; The two alleles have the same extra nucleotides.

e Indicates extra 9 nucleotides in the DNA sequence of allele 30.

These linkages demonstrate that sequence analysis of the ampC variants is probably a practical method to search for clinically significant clones of A. baumannii, as previously described for the intrinsic blaOXA-51-like gene [15, 16] However, the frequent occurrence of inter-strain exchanges of chromosomal segments should be taken into consideration. Therefore, analysis of ampC to study the epidemiology of A. baumannii should be complemented by characterizing other loci or preferably be taken within the context of whole-genome sequence analysis.

Updated list of the AmpC protein variants

In parallel, we revised and updated a previous collection of the AmpC variants (Table 2) [13]. As previously recommended, the AmpC variants were numbered according to the chronology of getting published and/or submitted to the INSDC databases. Numbers were preceded by a hyphen. When it was possible, numbers assigned by previous studies were retained. Accordingly, AmpC-1 was used to label the first AmpC protein variant reported in 2000 [2, 13]. The designation AmpC-72 (GenBank accession: AIL90389) was omitted since it showed 100% amino acid similarity to AmpC-70 (GenBank accession: KQG48886). Two variants with different amino acid sequences were designated as AmpC-57 (GenBank accessions: ADO51072 and AEZ36052). Subjectively, AmpC-57 was given to the variant detected in two A. baumannii isolates from East Africa [17]. New variants were defined, based on ≥ 1 amino acid substitution, and numbered under supervision of the INSDC curators. It is very important to re-emphasize that the AmpC variant numbers (Table 2) are not matching and not exchangeable with the ampC allele numbers (Table 1).

Table 2. Numeration of the AmpC protein variants encoded by Acinetobacter baumannii.

AmpC protein variant GenBank accession number Size (amino acid) NCBI reference sequence Other previous designations PubMed IDentifier (PMID) / GenBank submission authors
AmpC-1 (ADC-1) CAB77444 383 WP_004714775 ADC-NIPH 1362 10639377
AmpC-2 (ADC-2) AAO43172 383 WP_004746565 ADC-NIPH 1734 12709319
AmpC-3 AAO59456 383 WP_063857798 12709319
AmpC-4 AAO59457 383 WP_063857801 12709319
AmpC-5 CAE00827 383 WP_038405930 15047547
AmpC-6 AAR13676 383 WP_017725267 14742218
AmpC-7 AAT70411 383 WP_063857816 15980372
AmpC-10 ABI18382 388 WP_063857786 Hujer et al., unpublished
AmpC-11 ADG46039 383 WP_001211205 20713667; 16415984
AmpC-12 CAK95249 383 WP_063857787 19029333
AmpC-13 CAK95248 383 WP_063857788 19029333
AmpC-14 CAK95247 383 WP_063857789 19029333
AmpC-15 CAK95246 383 WP_063857790 19029333
AmpC-16 CAK95245 383 WP_063857791 19029333
AmpC-17 CAK95244 383 WP_063857792 19029333
AmpC-18 CAK95243 383 WP_002118772 19029333
AmpC-19 CAK95242 383 WP_063857793 19029333
AmpC-20 CAK95241 383 WP_063857794 19029333
AmpC-21 CAK95240 383 WP_063857795 19029333
AmpC-22 CAK95239 383 WP_063857796 19029333
AmpC-23 CAK95238 383 WP_063857797 19029333
AmpC-24 CAK95237 383 ADC-19 Beceiro & Bou., unpublished
AmpC-25 ABK34773 383 WP_001211217 ADC-NIPH 528 18077141
AmpC-26 ADG46043 383 WP_001211238 ADC-NIPH 146 20713667
AmpC-29 ACC66195 383 Chiu et al., unpublished
AmpC-30 ADG46041 383 WP_001211218 ADC-NIPH 2061 20713667
AmpC-31 ADX04315 383 WP_001211223 22038960
AmpC-32 ENU68675 383 WP_004739487 ADC-NIPH 615 24277043
AmpC-38 ACC95873 383 WP_063857799 18765689
AmpC-39 ACC95874 383 WP_063857800 18765689
AmpC-41 ACN62070 383 WP_063857802 20368407
AmpC-42 ACN62071 383 WP_063857803 20368407
AmpC-43 ACN62072 383 WP_032055358 20368407
AmpC-44 ACN62073 383 WP_063857804 20368407
AmpC-50 ADG46038 383 WP_031965243 Rodriguez-Martinez et al., unpublished
AmpC-51 ADG46040 383 WP_063857805 20713667
AmpC-52 ADG46042 383 WP_001211232 20713667
AmpC-53 ADG46044 383 WP_063857806 20713667
AmpC-54 ADK35761 383 WP_063857807 20805394
AmpC-56 AEL30570 383 WP_031973850 21788456
AmpC-57 ADO51072 383 WP_001211226 24176550
AmpC-58 AFG25594 383 WP_063857808 Zhang, unpublished
AmpC-59 AFG25595 383 WP_063857809 Zhang, unpublished
AmpC-60 AFH53180 383 WP_063857810 Huang, unpublished
AmpC protein variant GenBank accession number Size (amino acid) NCBI reference sequence Other previous designations PubMed IDentifier (PMID) / GenBank submission authors
AmpC-61 AFI56570 383 WP_033503051 Zhou, unpublished
AmpC-62 AFK24475 383 WP_063857811 Wang, unpublished
AmpC-63 AFM80040 383 WP_063857812 Zhang, unpublished
AmpC-65 AFP73417 385 Ling, unpublished
AmpC-66 AFP73418 383 Ling, unpublished
AmpC-67 AEZ36052 383 WP_063857814 ADC-57 Zhou, unpublished; 24619228
AmpC-68 AGL39360 383 WP_063857815 Lee et al., 2014 (as a poster); 25372683
AmpC-70 KQG48886 383 WP_017480710 ADC-72a Ozer et al., unpublished
AmpC-73 ALA14808 383 WP_001211219 26824943
AmpC-74 ALA14809 383 WP_001211203 26824943
AmpC-75 ALA14810 383 WP_063857817 26824943
AmpC-76 ALA14811 383 WP_001211237 ADC-NIPH 335 26824943
AmpC-77 ALA14812 383 WP_063857818 26824943
AmpC-78 ALA14813 383 WP_057691006 26824943
AmpC-79 ALA14814 383 WP_001159760 26824943
AmpC-80 ALA14815 383 WP_029424536 26824943
AmpC-81 ALA14816 388 WP_059262723 26824943
AmpC-82 AOA49613 383 Saranathan et al., unpublished
AmpC-83 ANW47146 383 Kulkarni et al., unpublished
AmpC-84 ANW47149 383 Kulkarni et al., unpublished
AmpC-85 ANW47142 383 Kulkarni et al., unpublished
AmpC-86 ANW47143 383 Kulkarni et al., unpublished
AmpC-87 ANW47154 383 Kulkarni et al., unpublished
AmpC-88 ANW47135 383 Kulkarni et al., unpublished
AmpC-89 ANW47136 383 Kulkarni et al., unpublished
AmpC-90 ANW47147 383 Kulkarni et al., unpublished
AmpC-91 ANW47132 383 Kulkarni et al., unpublished
AmpC-92 ANW47134 383 Kulkarni et al., unpublished
AmpC-93 ANW47145 383 Kulkarni et al., unpublished
AmpC-94 ANW47137 383 Kulkarni et al., unpublished
AmpC-95 ANW47153 383 Kulkarni et al., unpublished
AmpC-96 ANW47150 388 Kulkarni et al., unpublished
AmpC-97 ANW47139 383 Kulkarni et al., unpublished
AmpC-98 ANW47138 383 Kulkarni et al., unpublished
AmpC-99 ANW47140 383 Kulkarni et al., unpublished
AmpC-100 ANW47141 385 Kulkarni et al., unpublished
AmpC-101 ANW47133 383 Kulkarni et al., unpublished
AmpC-102 ANW47148 383 Kulkarni et al., unpublished
AmpC-103 ANW69905 383 Kulkarni et al., unpublished
AmpC-104 ANW69906 383 Kulkarni et al., unpublished
AmpC-105 ANW69907 383 Kulkarni et al., unpublished
AmpC-106 ANW69909 383 Kulkarni et al., unpublished
AmpC-107 ANW69912 383 Kulkarni et al., unpublished
AmpC-108 AFI94770 383 WP_001211216 22952140
AmpC-109 AAV32519 383 16441449
AmpC-110 ABO38124 383 Huang et al., unpublished
AmpC-111 ABV21800 384 WP_001211220 18591275
AmpC-112 ABV21801 383 18591275
AmpC-113 ABV21802 383 18591275
AmpC protein variant GenBank accession number Size (amino acid) NCBI reference sequence Other previous designations PubMed IDentifier (PMID) / GenBank submission authors
AmpC-114 ETY67158 384 20609238
AmpC-115 AFU38919 383 23209228
AmpC-116 WP_017816757 383 WP_017816757 23723398
AmpC-117 ELW88222 383 WP_002157727 Harkins et al., unpublished
AmpC-118 ENW75976 383 WP_001211227 ADC-CIP 70–34T 24277043
AmpC-119 ENU51112 383 WP_004712857 ADC-NIPH 1669 24277043
AmpC-120 ENV26641 383 WP_002126587 ADC-NIPH 190 24277043
AmpC-121 ENW36647 383 WP_005109685 ADC-NIPH 201 24277043
AmpC-122 ENW46489 383 WP_005123276 ADC-NIPH 329 24277043
AmpC-123 ENV30802 383 WP_004840559 ADC-NIPH 60 24277043
AmpC-124 ENW51893 383 WP_005128228 ADC-NIPH 601 24277043
AmpC-125 ENW51227 383 WP_005131186 ADC-NIPH 67 24277043
AmpC-126 ENW72863 383 WP_005138362 ADC-NIPH 80 24277043
AmpC-127 ENW00696 383 WP_005046018 ADC-CIP 81–8T 24277043
AmpC-128 ENU07956 383 WP_004643536 ADC-NIPH 13 24277043
AmpC-129 ENV92309 383 WP_005039111 ADC-ANC 3680 24277043
AmpC-130 ENV41121 383 WP_004886093 ADC-NIPH 386 24277043
AmpC-131 ENU48760 383 WP_004707701 ADC-NIPH 2119T 24277043
AmpC-132 ENW11417 383 WP_005068074 ADC-ANC 3678 24277043
AmpC-133 ENU43147 383 WP_004700205 ADC-NIPH 973 24277043
AmpC-134 ENX43770 383 WP_005307218 ADC-NIPH 542 24277043
AmpC-135 ENV03983 383 WP_004790939 ADC-NIPH 817 24277043
AmpC-136 EOQ64883 383 WP_016137488 ADC-ANC 3811 24277043
AmpC-137 EOQ71234 383 WP_016140427 ADC-ANC 4050 24277043
AmpC-138 EOQ73533 383 WP_016146025 ADC-ANC 4052 24277043
AmpC-139 EXS60093 383 WP_032039838 Harris et al., unpublished
AmpC-140 EYS55294 383 WP_001211209 Harris et al., unpublished
AmpC-141 EXD64655 383 WP_032062810 Harris et al., unpublished
AmpC-142 ETP95102 383 WP_031980335 24449752
AmpC-143 WP_033502167 383 WP_033502167 Liou et al., unpublished
AmpC-144 WP_001211214 383 WP_001211214 Sahl et al., unpublished
AmpC-145 KHY08585 383 WP_039270258 Adams et al., unpublished
AmpC-146 KHV30477 383 WP_039258389 Adams et al., unpublished
AmpC-147 KJC71195 383 WP_044718369 Adams et al., unpublished
AmpC-148 AJB47604 383 WP_039246976 McCorrison et al., unpublished
AmpC-149 ADY82440 383 WP_014207272 21441526
AmpC-150 AKT73351 383 WP_017386568 Ang et al., unpublished
AmpC-151 AMX20227 383 WP_063099318 Brasiliense et al., unpublished
AmpC-152 ADI89941 383 WP_013197184 20639327

a AmpC-70 has the same amino acid sequence as AmpC-72 (ADC-72) with the GenBank accession number AIL90389 and PubMed IDentifier 25181293

Concluding remarks

In our opinion, having two databases, one for the gene alleles and one for the protein variants, will create a lot of confusion. With the rapid accumulation of bacterial whole genome sequences, we argue that genes and alleles should reasonably be defined and numbered based on their nucleotide identities. For molecular epidemiological studies, the novel database for ampC in A. baumannii will provide unambiguous details beyond traditional list of AmpC variants that are limited to alleles with amino acid substitutions. To conclude, we emphasize on using the basic definition of the word “allele” for bacterial genes, by which novel alleles should be defined regardless if they are associated with amino acid changes or not.

Acknowledgments

We thank Dr. Daniel Haft at the National Center for Biotechnology Information (NCBI) for his advice and recommendations with regards to the list of AmpC protein variants.

Data Availability

The sequence data are available from Figshare (https://doi.org/10.6084/m9.figshare.4888283) and the pubmlst platform for A. baumannii (http://pubmlst.org/abaumannii/).

Funding Statement

This work was supported by project grants from the Swedish Research Council (VR-NT 2012-4638, VR-MH 2013-3878, and VR-MH 2015-03007) and The Kempe Foundations (JCK-1527). The work was performed as part of the Umeå Centre for Microbial Research (UCMR) Linnaeus Program supported by Umeå University and the Swedish Research Council (349-2007-8673). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The sequence data are available from Figshare (https://doi.org/10.6084/m9.figshare.4888283) and the pubmlst platform for A. baumannii (http://pubmlst.org/abaumannii/).


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