Table 2.
Antibiotic susceptibility profile and main antibiotic resistance related mutations detected among CC274 isolates.
| Isolate IDa | Antibiotic resistance profile (MIC values)b | Hyperexpression? | Main antibiotic resistance mutations encounteredc | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| TZ (≤8) | PM (≤8) | AT (≤1) | PPT (≤16) | C/T (≤4) | IP (≤4) | MP (≤2) | TO (≤4) | AK (≤8) | CI (≤0.5) | CO (≤2) | AmpC | MexAB | MexXY | ||
| AUS034* | > 256 | > 256 | > 256 | > 256 | 16 | > 32 | > 32 | 6 | > 256 | 1.5 | > 256 | + | − | + | gyrB (R441L), mexR (R85H), mexA (M1*), mexB (F178S, M555I), oprD(E264*), phoQ(E266*), parR (M59I), mexY(V1000L), mexZ(Nt334Δ13), fusA2(P329L), PA2489(R12L, A244T), mexS (P254Q), mexT(L157M), PBP4(W350R), capD (I7M, S51G), gyrA(T83I), mexK (S426G), mpl (Nt112ins1, V124G), fusA1 (V93A, P554L, D588G), rpoB (D831G, D964G), mexW (A627V, Q771P), PBP3 (P527T, G63S) |
| AUS410 | 4 | 24 | 1 | 12 | 4 | > 32 | > 32 | 64 | > 256 | 1 | 0.38 | − | − | + | gyrB (S466F), mexB(M552T), oprD (Nt583Δ1), lasR (A50V, D73G), sucC (V44G, A384V), oprF (Nt574Δ31), mexY (V32A), mexZ (Q164*), mexT (D327Y), mexE (F7Y), mpl (D168Y), PA2489(A125T, G185S, P260S), capD(I7M, S51G), fusA1(P618L), rpoC(E386K), mexW(Q511R), PBP3(G216S), pagL(Nt286Δ1), amgS(S64L) |
| AUS411 | > 256 | > 256 | > 256 | > 256 | 6 | > 32 | > 32 | > 256 | > 256 | 0.38 | 0.25 | − | − | + | gyrB (S466F), mexB (Q104E, F246C, L376V), phoQ (H248P), lasR (D73G), parS (D381E, T163N), sucC (C261G), mexY (D201A, G287A), PA2489 (R12L, A244T), fusA2 (I640L), mexE (V104G), htpX (Nt683Δ5), mexK (S426G), capD (I7M), fusA1 (K504E), rpoC (N690S), mexW (A627V,Q771P), PBP3 (Q372P), pagL (N159D) |
| AUS531 | 3 | 3 | 4 | 12 | 1 | 2 | 0.75 | 1 | 6 | 0.125 | 1 | − | − | − | PA2489 (R12L, A244T), capD (I7M, S51G), mexW (A627V, Q771P) |
| AUS588 | 2 | 8 | 3 | 8 | 1 | 1 | 0.75 | 1 | 8 | 0.125 | 0.75 | − | − | − | PA2489 (A125T, G185S, P260S), mexE (F7Y, V276M), capD (I7M), mexW (Q511R) |
| AUS601* | > 256 | > 256 | > 256 | 1 | 3 | > 32 | > 32 | 24 | > 256 | 16 | 0.25 | − | − | + | mexB (M552T), oprD (Nt1044ins4), phoQ (K234N, T315A), lasR (A50V), sucC (T102I, A384V), mexY (V32A), mexZ (Q164*), fusA2 (S445*), mexT(D327Y), mexE(F7Y), ftsK (A152V), PA2489 (A125T, G185S, P260S), capD (S51G), gyrA (T83I), mpl (G113D), fusA1 (P618L), rpoC (E386K), mexW (Q511R), PBP3 (R504C), pagL (E163G), pmrB (L31P), amgR (E204D) |
| AUS603 | 6 | 8 | 24 | 2 | 1.5 | > 32 | 8 | 1 | 8 | 0.25 | 1.5 | + | − | + | mexB (M552T), lasR (A50V, D73G), sucC (V44G, A384V), mexY (V32A), mexZ (Q164*), mexT (D327Y), mexE (F7Y), PA2489 (A125T, G185S, P260S), PBP4 (S315G), opmE (E204D), capD (I7M, Nt1438Δ1), mpl (Nt112ins1, Nt1317Δ1), fusA1 (P618L), mexW (Q511R) |
| AUS690* | 6 | 12 | 0.75 | 3 | 6 | 4 | 2 | 24 | > 256 | 12 | 0.125 | − | + | + | gyrB (Q467R), mexR (H133P), mexB (Nt712Δ1), phoP (T221I), lasR (T178I), parS (L10P), oprF (K250R), mexY (G402S, A850T), mexZ (Nt529Δ1), PA2489 (R12L, A244T), fusA2 (L104P, Nt889Δ1), htpX (G187D), capD (I7M, S51G), gyrA (T83A, T325I), mexK (G487E), mexH (Nt1086ins1), fusA1 (Y552C, T671I), rpoC (E136G, D616G, V808L), rpoB (F1046S), mexW (A627V, Q771P), pagL (P158L), pmrB (F124L), amgS (R188C), parE (P438S) |
| FQRC10 | 2 | 2 | 4 | 12 | 1 | 1.5 | 1 | 1 | 8 | 0.094 | 0.5 | − | − | − | PA2489 (R12L, A244T), capD (I7M, S51G), mexH (D356N), mexW (A627V, Q771P) |
| FQRC15 | 1 | 0.75 | 6 | 6 | 1 | 1.5 | 1 | 0.75 | 8 | 0.19 | 1 | − | − | − | PA2489 (R12L, A244T), capD (I7M), mexW (A627V, Q771P) |
| FQRC26 | 4 | 6 | 24 | 24 | 1 | 0.25 | 1.5 | 1 | 6 | 1.5 | 0.38 | − | + | − | mexY (V875M), mexT (R164H), PA2489 (R12L, A244T), capD (I7M, S51G), gyrA(Q106L), mexW (A627V, Q771P) |
| FQSE03 | 3 | 8 | 0.5 | 2 | 1.5 | 2 | 0.38 | 1 | 6 | 3 | 0.25 | − | − | + | mexA (L338P), lasR (P117G), mexZ (A144V), PA2489 (R12L, A244T), capD (I7M, S51G), gyrA (D87N), mexW (A627V, Q771P) |
| FQSE06-0403 | 0.75 | 2 | 0.25 | 4 | 0.38 | 1 | 0.5 | 24 | 16 | 0.19 | 0.19 | − | − | + | mexA (L338P), lasR (P117G), mexY (G287A), mexZ (S9P), PA2489 (R12L, A244T), mpl (S257L), capD (I7M, S51G), fusA1 (Y552C, T671I), mexW (A627V, Q771P), PBP3 (P215L), amgR (A8V) |
| FQSE06-1104* | 0.38 | 1 | 0.094 | 0.38 | 0.38 | 6 | 0.19 | 1 | 24 | 0.75 | 2 | − | − | + | mexA (L338P), lasR (P117G), mexZ (A194P), PA2489 (R12L, A244T), fusA2 (N236S, N561S), capD (I7M, S51G), gyrA (D87G), mexK (Q585*), rpoB (Y583C), mexW (A627V, Q771P), pmrB (V185I, G221D, R287Q), PBP1A (E161G), amgR (A8V) |
| FQSE06-0807 | 4 | 8 | 0.75 | 4 | 2 | 1.5 | 0.75 | 24 | >256 | 0.5 | 1 | − | − | + | mexA (L338P), lasR (P117G), mexY (G287A), mexZ (S9P), mexT (P270Q), PA2489 (R12L, A244T), mpl (S257L), capD (I7M, S51G), fusA1 (N482S, Y552C, T671I), mexW (A627V, Q771P), PBP3 (P215L), amgR (A8V) |
| FQSE06-0610 | 4 | 24 | 0.75 | 8 | 1.5 | 1 | 0.25 | 1.5 | 24 | 0.75 | 0.19 | − | − | + | mexA (L338P), lasR (P117G), mexZ (Nt290Δ11), PA2489 (R12L, A244T), mexW (A627V, Q771P), capD (I7M, S51G), amgR (A8V) |
| FQSE10-0503 | 1.5 | 12 | 4 | 4 | 1.5 | 1 | 0.25 | 0.75 | 8 | 0.25 | 0.25 | − | − | + | mexY (V875M, N1036S), mexZ (IS), PA2489 (R12L, A244T), ftsK (A38T), nalD (Nt459Δ13), mexW (A627V, Q771P), capD (I7M, S51G) |
| FQSE10-0106 | 0.75 | 3 | 0.125 | 0.75 | 0.5 | 0.38 | 0.032 | 0.75 | 4 | 0.38 | 1.5 | − | − | + | mexB (L738P), mexY (V875M, N1036S), mexZ (IS), PA2489 (R12L, A244T), ftsK(A38T), capD (S51G), nalD (Nt396Δ2), mexW (A627V, Q771P), nfxB (*188ext) |
| FQSE10-0110 | 3 | 8 | 16 | 8 | 2 | 1 | 0.125 | 0.75 | 4 | 0.75 | 0.5 | − | + | + | mexY (V875M, N1036S), mexZ (IS), PA2489 (R12L, A244T), ftsK (A38T), rpoB (D659E, E904K), mexW (A627V, Q771P), pmrB (R287Q) |
| FQSE10-0111 | 3 | 16 | 12 | 12 | 8 | 1.5 | 1 | 1 | 12 | 0.38 | 0.38 | − | − | + | mexY (V875M, N1036S), mexZ (IS), PA2489 (R12L, A244T), ftsK (A38T, D54Y), capD (S51G), mexW (A627V, Q771P) |
| FQSE15-0803 | 2 | 12 | 0.38 | 4 | 1.5 | 6 | 1 | 1 | 12 | 0.19 | 0.25 | − | − | + | mexA (L338P), lasR (P117G), mexZ (A144V), PA2489 (R12L, A244T), capD (I7M, S51G), pmrB (E213D), mexW (A627V, Q771P), amgR (A8V) |
| FQSE15-0906 | 0.75 | 6 | 0.38 | 2 | 1 | 1 | 0.047 | 1.5 | 12 | 0.38 | 0.75 | − | − | + | mexA (L338P), lasR (P117G), mexZ (A144V), mexS (Nt848Δ2), mexT (Nt534Δ17), PA2489 (R12L, A244T), capD (I7M, S51G), mexK (S426G), mexW (A627V, Q771P), amgR (A8V) |
| FQSE15-0310 | 1 | 4 | 1 | 1 | 1 | 12 | 0.19 | 1 | 8 | 0.38 | 0.25 | − | − | + | mexA (L338P), lasR (P117G), mexZ (A144V), mexS (Nt848Δ2), mexT (Nt534Δ17), PA2489 (R12L, A244T), capD (I7M, S51G), mexK (P834S), mpl (Nt1266Δ1), rpoC (Nt1181Δ3), mexW (A627V, Q771P), amgR (A8V) |
| FQSE15-1110* | 8 | 24 | 6 | 4 | 1 | >32 | >32 | 1 | 16 | 1 | 0.25 | − | − | + | gyrB (S466F), mexA (N71S, D235G), mexB (L376V), oprD (V67*), lasR (P117G), mexY (Y355H), mexZ (A194P), galU (P123L), PA2050 (G90R, Q161R), PA2489 (R12L, A244T), fusA2 (N236S, N561S), htpX (A141T), capD (I7M, S51G), fusA1 (K430E), rpoC (V693A), mexW (A627V, Q771P), pmrB (R287Q), PBP1A (E161G), amgS (D267N), amgR (A8V) |
| FQSE24-0304* | 2 | 24 | 0.38 | 8 | 1 | >32 | >32 | 2 | 24 | 6 | 0.38 | − | − | + | gyrB (S466F), mexA (L338P), oprD (V67*), lasR (P117G), mexY (Y355H), mexZ (A194P), galU (P123L), PA2050 (G90R, Q161R), PA2489 (R12L, A244T), fusA2 (N236S, N561S), opmE (D421G), capD (I7M, S51G), fusA1 (K430E), rpoC (V693A), mexW (A627V, Q771P), pmrB (R287Q), PBP1A (E161G), amgR (A8V) |
| FQSE24-1005* | 1 | 16 | 0.38 | 2 | 1.5 | >32 | 8 | 3 | 16 | 6 | 1 | − | − | + | gyrB (S466F), oprD (V67*), lasR (P117G), mexY (Y355H), mexZ (A194P), galU (P123L), PA2050 (G90R, Q161R), fusA2 (N236S, N561S), PA2489 (R12L, A244T), fusA1 (K430E), rpoC(V693A), mexW (A627V, Q771P), pmrB (R287Q), PBP1A (E161G, R407S), amgR (A8V) |
| FQSE24-0308* | 1 | 8 | 0.25 | 0.75 | 1.5 | >32 | 0.25 | 2 | 16 | 4 | 1 | − | − | + | gyrB (S466F), oprD (V67*), lasR (P117G), mexY (Y355H), mexZ (A194P), galU (P123L), PA2050 (G90R, Q161R), fusA2 (N236S, N561S), PA2489 (R12L, A244T), capD (I7M, S51G), fusA1 (K430E), rpoC (V693A), mexW (A627V, Q771P), pmrB (R287Q), PBP1A (E161G), amgS (T92A), amgR(A8V) |
| FQSE24-1010* | 1 | 8 | 1 | 1 | 1 | >32 | 4 | 4 | 64 | 4 | 0.38 | − | − | + | gyrB (S466F), mexA (L338P), oprD (V67*), lasR (P117G), mexY (Y355H), mexZ (A194P), galU (P123L), PA2050 (G90R, P97L, Q161R), PA2489 (R12L, A244T), fusA2 (N236S, N561S), opmE (L400P, D421G), mexH (V221I), capD (I7M, S51G, A165V), fusA1 (K430E), rpoC(V693A), mexW (A627V, Q771P), PBP3 (G216S), pmrB (R287Q), PBP1A (E161G), amgS (A13V), amgR (A8V) |
| PAMB148 | >256 | 64 | >256 | >256 | 6 | 1.5 | 0.75 | 1.5 | 16 | 0.064 | 0.5 | + | − | − | PA2489 (R12L, A244T), capD (I7M, S51G), mexY (V875M, N1036S), mexW (A627V, Q771P), ampD (P41L) |
| % I + R | 13.8 | 44.8 | 48.3 | 13.8 | 17.2 | 44.8 | 27.6 | 24.1 | 62.1 | 48.3 | 3.4 | ||||
aIsolates are labelled according to the following format: Patient identification - MMYY isolation code in the case of sequential isolates. Mutators isolates are identified with and asterisk.
bMinimal Inhibitory Concentration (MIC) values were determined by grading MIC testing for the following antimicrobial agents: ceftazidime (TZ); cefepime (PM); aztreonam (AT); piperacillin-tazobactam (PPT); cefotolozane-tazobactam (C/T); imipenem (IP); meropenem (MP); tobramycin (TO); amikacin (AK); ciprofloxacin (CI) and colistin (CO). Clinical breakpoints established by EUCAST v7.0 for each antibiotic are shown in brackets.
cThe main antibiotic resistance related mutations documented for each isolate are shown. For this purpose, the full list of mutations in the 164 genes studied (available in Supplementary Data Set S1) was refined to include only those more likely to be involved in the resistance phenotypes, by including: (i) mutations with known effect on resistance according to published evidence (ii) mutations for which our experimental evidence crosslinks resistance phenotypes and genotypes (e.g. mutations in genes involved in AmpC, efflux or OprD regulation and β-lactam resistance phenotypes are crosslinked by integrating the analysis of the expression of ampC, efflux pumps genes and oprD and/or (ii) mutations in genes found to be under high evolutionary pressure (those with at least 3 different mutational events documented).