Sublethal Sodium Hypochlorite Exposure: Impact on Resistance-Nodulation-Cell Division Efflux Pump Overexpression and Cross-Resistance to Imipenem
Abstract
:1. Introduction
2. Results
2.1. Effect of Exposure to Disinfectants on Gram-Negative Bacteria
2.2. Antibiotic Susceptibility Was Reduced According to NaOCl Exposure
2.3. Cross-Resistance between NaOCl Disinfectant and β-Lactams in Klebsiella pneumoniae
2.4. Cross-Resistance between NaOCl Disinfectant and β-Lactams in Pseudomonas aeruginosa
3. Discussion
4. Materials and Methods
4.1. Isolation and Identification of Bacterial Strains
4.2. Determination of Antibiotic and Disinfectant Minimum Inhibitory Concentrations (MICs)
4.3. NaOCl Disinfectant Exposure and Bacterial Subculturing
4.4. RNA Extraction, Transcriptome Sequencing, and Quantitative Reverse Transcription Polymerase Chain Reaction
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Species | Strains | MICs (mg/L) | Antibiotic Susceptibility (Exposure to 1250 µg/mL NaOCl) | |||
---|---|---|---|---|---|---|
Before 1 | After | Increased | Reduced | |||
K. pneumoniae | CRKP * | Z0317KP0159 | 500 | 2500 | FOX, IMI, CHL † | ND 2 |
Z0317KP0181 | 500 | 2500 | IMI | GEN ‡ | ||
Z0318KP0099 | 500 | 2500 | IMI | STR | ||
Z0318KP0107 | 500 | 2500 | IMI, CHL, AZI | ND | ||
Z0318KP0236 | 500 | 2500 | IMI, CHL | GEN, AZI | ||
P. aeruginosa | CSPA | ATCC 27853 | 500 | 2500 | AXO, IMI, STR, COL | TAZ, CIP, NAL, TET, GEN, AMI, SXT |
Z0219PA0007 | 500 | 1250 | AXO, IMI, COL | CIP, NAL, STR, SXT | ||
CRPA | I0020PA0021 (HL-IMI) | 500 | 2500 | X 3 | X | |
I0020PA0028 | 500 | 1250 | IMI, CIP, NAL, TET, AMI, STR | FOT, TAZ, AXO, GEN | ||
Z0217PA0020 (HL-IMI) | 500 | 2500 | FOT, TAZ, CIP, CHL, GEN, STR, SXT | NAL, AMI |
Group | Function | Gene Locus Tag (Gene Name) | Gene Expression Fold Change * | |
---|---|---|---|---|
Z0317 KP0159 | Z0318 KP0107 | |||
Enzymatic degradation | Class A carbapenemase Kpc-2 | KPHS_p200360 (blaKPC-2) | −2.26 | 3.40 |
β-lactamase | KPHS_25220 (blaSHV) | 2.43 | −1.44 | |
KPHS_13880 | - | 2.71 | ||
RND efflux pump | Repression of porin OmpF (mar-sox-rob regulon activator) | KPHS_25470 (marA) | −1.44 | 67.73 |
Multidrug efflux membrane fusion protein | KPHS_11890 (acrA) | 1.46 | 5.18 | |
Multidrug efflux transporter | KPHS_11880 (acrB) | 2.19 | 2.30 | |
Multidrug efflux transporter (permease EefB) | KPHS_52090 (acrB) | 2.07 | 2.65 | |
Outer membrane channel protein | KPHS_45760 (tolC) | 2.83 | 1.30 | |
Multidrug efflux transport outer membrane protein EefC | KPHS_52100 (adeK) | 2.13 | −1.16 | |
Porin | Outer membrane protein 1A/OmpK35 porin | KPHS_18370 (ompF) | −2.45 | 1.52 |
Outer membrane pore protein C/OmpK36 porin | KPHS_37010 (ompC) | - | 2.22 |
Group | Function | Gene Locus Tag (Gene Name) | Gene Expression Fold Change * | |||
---|---|---|---|---|---|---|
ATCC 27853 | Z0219 PA0007 | Z0217 PA0020 | ||||
β- lactamase | AmpC beta-lactamase | PA4110 (ampC) | - | −2.32 | −1.07 | |
Beta-hexosaminidase | PA3005 (nagZ) | 4.30 | - | - | ||
Transport of degraded muropeptides (GlcNAc-anhMurNAc) | PA4218 (ampG) | −6.95 | 13.74 | 1.92 | ||
RND efflux pump | MexAB-OprM | MexR anti-repressor ArmR | PA3719 (armR) | - | 2.29 | 3.87 |
Transcriptional regulator AmpR | PA4109 (ampR) | - | 2.31 | 2.62 | ||
Transcriptional regulator | PA3721 (nalC) | −2.65 | - | - | ||
Transcriptional regulator | PA3574 (nalD) | −2.39 | −2.33 | −1.75 | ||
Multidrug resistance protein MexA | PA0425 (mexA) | - | 2.50 | 2.03 | ||
Multidrug resistance protein MexB | PA0426, PA4375 (mexB) | - | 2.75 | 3.09 | ||
Outer membrane protein OprM | PA0427 (oprM) | - | 2.09 | 3.06 | ||
MexEF-OprN | Multidrug efflux membrane fusion protein MexE | PA2493 (mexE) | 11.88 | - | - | |
Multidrug efflux transporter MexF | PA2494 (mexF) | 4.11 | - | - | ||
Transcriptional regulator AmpR | PA2495 (oprN) | 9.75 | - | - | ||
MexXY-(OprM) | Transcriptional regulator | PA2020 (mexZ) | - | 2.84 | −2.21 | |
Two-component response regulator ParR | PA1799 (parR) | −7.73 | −2.53 | −2.06 | ||
Multidrug efflux membrane fusion protein | PA2019 (mexX) | 4.04 | 20.45 | 8.88 | ||
Multidrug efflux transporter | PA2018 (mexY) | 2.32 | 21.02 | 8.00 | ||
Outer membrane protein | PA4144 (oprM) | 2.64 | 1.11 | −2.13 | ||
MexZ anti-repressor | PA5471 (armZ) | 9.59 | 4.59 | 10.34 | ||
MexVW-OprM | Multidrug efflux membrane fusion protein MexV | PA4374 (mexV) | - | - | - | |
Multidrug efflux membrane protein | PA4375 (mexW) | - | 1.31 | 2.62 | ||
Outer membrane protein OprM | PA4974 (oprM) | - | −2.63 | 5.65 | ||
Porin | Porin D (imipenem) | PA0958 (oprD) | - | - | 2.91 |
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Nam, J.-H.; Yoo, J.S. Sublethal Sodium Hypochlorite Exposure: Impact on Resistance-Nodulation-Cell Division Efflux Pump Overexpression and Cross-Resistance to Imipenem. Antibiotics 2024, 13, 828. https://doi.org/10.3390/antibiotics13090828
Nam J-H, Yoo JS. Sublethal Sodium Hypochlorite Exposure: Impact on Resistance-Nodulation-Cell Division Efflux Pump Overexpression and Cross-Resistance to Imipenem. Antibiotics. 2024; 13(9):828. https://doi.org/10.3390/antibiotics13090828
Chicago/Turabian StyleNam, Ji-Hyun, and Jung Sik Yoo. 2024. "Sublethal Sodium Hypochlorite Exposure: Impact on Resistance-Nodulation-Cell Division Efflux Pump Overexpression and Cross-Resistance to Imipenem" Antibiotics 13, no. 9: 828. https://doi.org/10.3390/antibiotics13090828