Characterization of Haemophilus influenzae Strains with Non-Enzymatic Resistance to β-Lactam Antibiotics Caused by Mutations in the PBP3 Gene in the Czech Republic in 2010–2018
Abstract
:1. Introduction
2. Results
2.1. Phenotypic Detection
2.2. PCR and Mutation of the ftsI Gene
2.3. MLST, CC
3. Discussion
4. Materials and Methods
4.1. Strains
4.2. Susceptibility Testing to β-Lactams
4.3. PCR Detection of β-Lactamases
4.4. Detection of Mutations in the ftsI Gene and Comparative Analysis
4.5. Multi-Locus Sequence Typing (MLST) and Clonal Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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β-Lactamase Negative | β-Lactamase Positive | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Range of Measured Values | MLST | Range of Measured Values | MLST | |||||||||||
PBP3 Groups | AA Substitutions and Their Combinations | N | MIC AMP c (mg/L) | MIC CTX (mg/L) | PEN (mm) | AMC (mm) | CRX (mm) | AMP MIC50/MIC90 (mg/L) | ST/CC * a | N | MIC CTX (mg/L) | AMC (mm) | CRX (mm) | ST/CC * a |
sPBP3 (n = 12) | A502S | 1 | 1 | 0.06 | 12 | 15 | 26 | 1/1 | 1218/1218 | |||||
V511A | 1 | 0.06 | 11 | 23 | 426 | |||||||||
D350N | 6 | 0.25–1 | 0.016–0.03 | 12–16 | 17–21 | 26–28 | 0.25/0.5 | 124 (5), 145/11 | 3 | 0.016 | 15–16 | 21–29 | 388 (3) | |
A388V | 1 | 0.03 | 17 | 27 | 401 | |||||||||
rPBP3 Group I (n = 15) | A502V, R517H | 13 | 1–4 | 0.03–0.125 | 6–19 | 12–19 | 14–27 | 2/4 | 1218/1218 (11), 1840/1218, 1841/1218 | 2 b | 0.016–0.06 | 13–19 | 23–31 | 146, 1218/1218 |
rPBP3 Group II (n = 175) | A368T, A502T, N526K | 2 | 1–4 | 0.06 | 6–11 | 17 | 20–23 | 1/4 | 950, 1825 | |||||
A502T, N526K | 1 | 2 | 0.125 | 6 | 13 | 21 | 2 | 12 | ||||||
A502V, N526K | 5 | 1–2 | 0.03–0.06 | 6–11 | 11–15 | 21–25 | 2/2 | 142 (2), 411/422 (3) | 2 | 0.03–0.06 | 10–14 | 21–23 | 34, 411/422 | |
D350N, A437S, A502V, N526K | 6 | 1–4 | 0.03–0.06 | 6–11 | 9–16 | 15–23 | 2/4 | 196 (5), 1837 | 2 | 0.03–0.06 | 10–13 | 17–23 | 836 (2) | |
D350N, A437S, G490E, N526K, A530S | 1 | 4 | 0.06 | 6 | 7 | 21 | 1 | 390 | ||||||
D350N, A502T, N526K | 8 | 1–4 | 0.06–0.125 | 6–11 | 10–14 | 6–21 | 2/4 | 183 (2), 1362, 1820, 1025 (4) | 1 | 0.06 | 9 | 19 | 1860/396 | |
D350N, A502V, N526K | 1 | 4 | 0.06 | 10 | 14 | 22 | 4 | 122 | ||||||
D350N, G490E, A502V, N526K | 1 | 2 | 0.03 | 9 | 15 | 21 | 2 | 2457 | ||||||
D350N, G490E, A502V, N526K, A530S | 1 | 0.25 | 6 | 12 | 836 | |||||||||
D350N, G490E, N526K, A530S | 18 | 0.25–4 | 0.008–0.06 | 6–11 | 10–18 | 17–25 | 2/4 | 107 (14), 159/1218, 201, 203, 425 | ||||||
D350N, I449V, N526K | 1 | 1 | 0.03 | 12 | 16 | 24 | 1 | 152 | ||||||
D350N, M377I, A502V, N526K | 74 | 0.25–16 | 0.016–0.125 | 6–11 | 6–20 | 11–29 | 2/8 | 14/14 (13), 98, 124, 136/367 (2), 145/11, 165 (6), 203 (3), 262, 367/367 (2), 422/422, 1034/14 (47), 1206/14 (2), 1218/1218 | 6 | 0.03–0.125 | 6–14 | 15–23 | 165 (5), 1206/14 | |
D350N, M377I, G490E, A502V, N526K | 6 | 1 | 0.03–0.06 | 6–11 | 10–14 | 18–21 | 1/1 | 33, 556, 834, 844 (3) | ||||||
D350N, M377I, I491V, A502V, N526K | 1 | 4 | 0.125 | 6 | 10 | 18 | 4 | 1034/14 | ||||||
D350N, S357N, A502V, N526K | 1 | 2 | 0.125 | 9 | 12 | 17 | 2 | 1822/422 | ||||||
G490E, N526K, A530S | 1 | 2 | 0.125 | 9 | 12 | 19 | 2 | 1858/1218 | ||||||
G490E; A502V; N526K | 1 | 2 | 0.06 | 10 | 14 | 17 | 2 | 85 | ||||||
I449V, N526K | 17 | 1–4 | 0.03–0.06 | 6–10 | 9–15 | 15–27 | 2/4 | 57, 253 (4), 390, 396/396 (7), 687/396, 695/396, 1202/396, 2458 | ||||||
M377I, A502V, N526K | 3 | 0.03–0.06 | 11–15 | 19–20 | 165 (3) | |||||||||
M377I, I449V, N526K | 5 | 1–4 | 0.06–0.25 | 6 | 6–14 | 12–19 | 4/4 | 11/11 (3), 1826/11, 2032/11 | ||||||
N526K | 3 | 0.5–4 | 0.03–0.06 | 8–11 | 13–17 | 19–27 | 1/4 | 34 (3), | ||||||
N526K, A530S | 5 | 1–4 | 0.06–0.125 | 6–11 | 12–17 | 17–25 | 2/4 | 2459, 142 (4) | ||||||
R501L, N526K | 2 | 1 | 0.06 | 6–8 | 12–13 | 19–24 | 1/1 | 196 (2) | ||||||
rPBP3 Group III (n = 26) | D350N, M377I, S385T, L389F, I519L, N526K | 1 | 4 | 0.5 | 6 | 6 | 6 | 4 | 2044 | |||||
D350N, S357N, M377I, S385T, L389F, G490E, N526K, A530S | 2 | 4–8 | 0.5 | 6 | 6–12 | 6–12 | 4/8 | 107, 1859 | 2 | 0.5 | 6–16 | 8–16 | 107 (2) | |
D350N, S357N, M377I, S385T, L389F, N526K | 2 | 4–16 | 1 | 6 | 6 | 6 | 4/16 | 472 (2) | ||||||
D350N, S357N, M377I, S385T, L389F, P393L, R517H, T532S | 1 | 1 | 6 | 6 | 388 | |||||||||
D350N, S357N, M377I, S385T, L389F, R517H | 1 | 1 | 12 | 16 | 422/422 | |||||||||
D350N, S357N, M377I, S385T, R517H, T532S | 5 | 1–8 | 0.125–1 | 6–11 | 8–15 | 6–21 | 4/8 | 57, 155 (2), 1857, 2031/367 | ||||||
D350N, S357N, M377I, S385T, L389F, R517H, T532S | 3 | 16 | 1–2 | 6 | 6–11 | 6–17 | 16/16 | 142, 264, 2043 | 6 | 1–2 | 6–12 | 6 | 3/367, 103/11 (2), 160, 1521, 1824 | |
M377I, S385T, L389F, R517H | 1 | 8 | 1 | 6 | 6 | 6 | 8/8 | 142 | 1 | 1 | 6 | 6 | 1836 | |
V329I, D350N, S357N, M377I, S385T, L389F, N526K | 1 | 8 | 2 | 6 | 13 | 15 | 8/8 | 1609 |
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Jakubu, V.; Malisova, L.; Musilek, M.; Pomorska, K.; Zemlickova, H. Characterization of Haemophilus influenzae Strains with Non-Enzymatic Resistance to β-Lactam Antibiotics Caused by Mutations in the PBP3 Gene in the Czech Republic in 2010–2018. Life 2021, 11, 1260. https://doi.org/10.3390/life11111260
Jakubu V, Malisova L, Musilek M, Pomorska K, Zemlickova H. Characterization of Haemophilus influenzae Strains with Non-Enzymatic Resistance to β-Lactam Antibiotics Caused by Mutations in the PBP3 Gene in the Czech Republic in 2010–2018. Life. 2021; 11(11):1260. https://doi.org/10.3390/life11111260
Chicago/Turabian StyleJakubu, Vladislav, Lucia Malisova, Martin Musilek, Katarina Pomorska, and Helena Zemlickova. 2021. "Characterization of Haemophilus influenzae Strains with Non-Enzymatic Resistance to β-Lactam Antibiotics Caused by Mutations in the PBP3 Gene in the Czech Republic in 2010–2018" Life 11, no. 11: 1260. https://doi.org/10.3390/life11111260
APA StyleJakubu, V., Malisova, L., Musilek, M., Pomorska, K., & Zemlickova, H. (2021). Characterization of Haemophilus influenzae Strains with Non-Enzymatic Resistance to β-Lactam Antibiotics Caused by Mutations in the PBP3 Gene in the Czech Republic in 2010–2018. Life, 11(11), 1260. https://doi.org/10.3390/life11111260