Differential Proteomic and Genomic Comparison of Resistance Mechanism of <i>Pseudomonas aeruginosa </i>to Cefoperazone Sodium/Sulbactam Sodium

CAI, SHUANGQI; ZHANG, KEXING; WEI, FEI; YANG, LEI; SONG, DEZHI; LUO, JIN; HUANG, HONG; GAO, XINGXIN; DU, GANG; KONG, JINLIANG; CHEN, YIQIANG

doi:10.1590/0001-3765202220211160

SHUANGQI CAI

First Affiliated Hospital of Guangxi Medical University, No. 22, Shuangyong Road, Nanning, 530000, Guangxi, China

https://orcid.org/0000-0002-3340-5405

KEXING ZHANG

The First Affiliated Hospital of Guangxi University of Chinese Medicine, No.89-9, Dongge Road, Nanning, 530000, Guangxi, China

https://orcid.org/0000-0002-2320-9726

FEI WEI

The First People’s Hospital of Nanning, NO.69, Qixing Road, 530000, Nanning, Guangxi, China

https://orcid.org/0000-0003-0815-4971

LEI YANG

The First Affiliated Hospital of Guangxi University of Chinese Medicine, No.89-9, Dongge Road, Nanning, 530000, Guangxi, China

https://orcid.org/0000-0001-8186-9338

DEZHI SONG

First Affiliated Hospital of Guangxi Medical University, No. 22, Shuangyong Road, Nanning, 530000, Guangxi, China

https://orcid.org/0000-0001-9431-5182

JIN LUO

First Affiliated Hospital of Guangxi Medical University, No. 22, Shuangyong Road, Nanning, 530000, Guangxi, China

https://orcid.org/0000-0002-8186-4745

HONG HUANG

First Affiliated Hospital of Guangxi Medical University, No. 22, Shuangyong Road, Nanning, 530000, Guangxi, China

https://orcid.org/0000-0001-6428-1364

XINGXIN GAO

First Affiliated Hospital of Guangxi Medical University, No. 22, Shuangyong Road, Nanning, 530000, Guangxi, China

https://orcid.org/0000-0001-5970-3606

GANG DU

First Affiliated Hospital of Guangxi Medical University, No. 22, Shuangyong Road, Nanning, 530000, Guangxi, China

https://orcid.org/0000-0002-8446-6881

JINLIANG KONG

First Affiliated Hospital of Guangxi Medical University, No. 22, Shuangyong Road, Nanning, 530000, Guangxi, China

https://orcid.org/0000-0003-4065-7886

YIQIANG CHEN

First Affiliated Hospital of Guangxi Medical University, No. 22, Shuangyong Road, Nanning, 530000, Guangxi, China

https://orcid.org/0000-0003-1788-4079

#These authors contributed equally to this work. Correspondence to: Yiqiang Chen, Jinliang Kong E-mail: 2667455027@qq.com, 158514904@qq.com

AUTHOR CONTRIBUTIONS

Analysis and interpretation of data: Shuangqi Cai, Kexing Zhang. Conception and design of the study: Fei Wei. Drafting the article: Lei Yang. Revising it critically for important intellectual content: Dezhi Song, Jin Luo, Hong Huang. Acquisition of data:Xingxin Gao, Gang Du. Final approval of the version to be submitted: Jinliang Kong, Yiqiang Chen.

Figures (5)
Tables (1)

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Figure 1
Detection rates of P. aeruginosa in hospital departments between 2013 and 2015. We detected 3,556 strains of P. aeruginosa between 2013–2015, mostly in Departments of Burns and Chinese Medicine, and ICU-1.

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Figure 2
Analysis of P. aeruginosa resistance to cefoperazone sodium/sulbactam sodium of hospital-wide during 2013–2015. Hospital-wide resistance of P. aeruginosa strains to cefoperazone sodium/sulbactam sodium slightly increased during 2013–2015 (resistance rates: 21.2%, 21.5%, and 24.6%, respectively). Compared with hospital-wide resistant P. aeruginosa strains, EICU, Neurosurgery Division, ICU-1, ICU-2, Department of Chinese Medicine, Department of Burns, PICU, and NICU had relatively higher rates.

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Figure 3
Protein fingerprint analysis by mass spectrometry. a) We detected 242 protein peaks for PAO1 bacteriophage proteins in induced drug-resistant (DR) PAO1 (DR) and wild-type (WT) groups (P < 0.05). b) Expression of 26 and 15 proteins was upregulated and downloaded, respectively, in DR, compared with WT PAO1.

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Figure 4
Distribution of library fragment peak. The WT group contained 679 mutant loci. The Figure shows that the main peak among library fragments was 330 bp, and the molar concentration was 2,999 pmol/L.

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Figure 5
Mutant loci distribution in WT and DR P. aeruginosa samples. Analysis of single nucleotide polymorphisms (SNPs) using Freebayes software (Biomatters Ltd., Auckland, NZ) revealed 141 (5%) and 792 (15.6%) common mutant loci in three WT (ID numbers: 011, 012, 013) and three DR (ID numbers: 014, 015, and 016) samples with Q (quality) values ≥ 20. The DR group contained 679 loci. Regardless of the numbers of common mutation sites or the total number of mutation sites, the DR group contained significantly more sites than the WT group (P < 0.05).

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Table I
Mutated genes in P. aeruginosa are resistant to cefoperazone sodium/sulbactam sodium.

Gene ID	Name	Type of mutation	Sequence (Control group)	Sequence (Observation group)
880778	coaB	Substitution mutation	5’-TCCTGGCCGTTGCCGGCCTGA-3’	5’-TCCTGGCCGTCGCCGGCCTGA-3’
878952	lipB	Frameshift mutation	5’-TCCCGGCGTAGCCGCAGGGAT-3’	5’-TCCCGGCGTAGCGCAGGGAT-3’
879090	PA3789	Frameshift mutation	5’-TGGCGCGGATCGTCGGGGAAC-3’	5’-TGGCGCGGATCTCGGGGAAC-3’
880817	tyrZ	Frameshift mutation	5’-CTTCCGCAAGGACGTCGAGGC-3’	5’-CTTCCGCAAGGCGTCGAGGC-3’
881949	PA1576	Substitution mutation	5’-GCAAGGGCGCGGCCCAGTCCT-3’	5’-GCAAGGGCGCCGCCCAGTCCT-3’
877727	mtr	Substitution mutation	5’-TGAGCAACGCTTTCAGCGAAT-3’	5’-TGAGCAACGCGTTCAGCGAAT-3’
878655	corA	Frameshift mutation	5’-TGGCGGATGCAGCGGTTCTCG-3’	5’-TGGCGGATGCACGGTTCTCG-3’
880657	betC	Frameshift mutation	5’-GAAGTCCAGCTGGTTGGTGCG-3’	5’-GAAGTCCAGCTGTTGGTGCG-3’
881860	fliM	Frameshift mutation	5’-TGGCCAACATCGTCAGTCCCA-3’	5’-TGGCCAACATCTCAGTCCCA-3’
878041	PA0793	Frameshift mutation	5’-CCGGCTGGCTGCTCTTCGAGA-3’	5’-CCGGCTGGCTGTCTTCGAGA-3’
880269	PA0726	Substitution mutation	5’-GCCAGCATCGTTCCGGCAGCG-3’	5’-GCCAGCATCGCTCCGGCAGCG-3’
880742	PA0727	Substitution mutation	5’-CGACCCTGAACGGGGATCCGT-3’	5’-CGACCCTGAATGGGGATCCGT-3’
878199	PA5475	Frameshift mutation	5’-AGACCCTGGTAGTCGTCGGCG-3’	5’-AGACCCTGGTATCGTCGGCG-3’
882536	trkH	Frameshift mutation	5’-TCCTGCCGGGACGTCCCGAGC-3’	5’-TCCTGCCGGGAGTCCCGAGC-3’
880269	PA0726	Substitution mutation	5’-GGCTGCTCCAACGCGTCCTGC-3’	5’-GGCTGCTCCAGCGCGTCCTGC-3’
880742	PA0727	Substitution mutation	5’-TGGAAACGGTCTGGCGGCTCG-3’	5’-TGGAAACGGTGTGGCGGCTCG-3’
878199	PA5475	Frameshift mutation	5’-TCTGGCGGAAGCCGTTGCGCC-3’	5’-TCTGGCGGAAGCGTTGCGCG-3’
882583	wbpM	Frameshift mutation	5’-TGCACAGCAGAGTACCAGTCT-3’	5’-TGCACAGCAGATACCAGTCT-3’
880269	PA0726	Substitution mutation	5’-TCCGCAGACGCACCGGCCAGG-3’	5’-TCCGCAGACGTACCGGCCAGG-3’
880777	PA0724	Substitution mutation	5’-CAGTTGCTATCTGGTCAAAGG-3’	5’-CAGTTGCTATTTGGTCAAAGG-3’
880749	cdhR	Frameshift mutation	5’-AGCCATCGACGCCTTCCAGGA-3’	5’-AGCCATCGACGCTTCCAGGA-3’
879629	PA5078	Frameshift mutation	5’-ACGAAGCGGTAGGCGCCGGTG-3’	5’-ACGAAGCGGTAGCGCCGGTG-3’
880269	PA0726	Substitution mutation	5’-CGGGAGGCAGCCCGGCGCGGT-3’	5’-CGGGAGGCAGGCCGGCGCGGT-3’
880777	PA0724	Substitution mutation	5’-GCGGTGCCGATTCCTACACCT-3’	5’-GCGGTGCCGACTCCTACACCT-3’
880393	PA0446	Frameshift mutation	5’-GGCGAACTTGCGGAACTGGCT-3’	5’-GGCGAACTTGCGAACTGGCT-3’
879479	trpA	Frameshift mutation	5’-TTCGCCTCGGCGATGAAGCGT-3’	5’-TTCGCCTCGGCATGAAGCGT-3’
879244	dnaN	Frameshift mutation	5’-CCGAGCAGGACGGCGAAGTCG-3’	5’-CCGAGCAGGACGCGAAGTCG-3’
880777	PA0724	Substitution mutation	5’-CGCTGCTGCTGATGGCCGCGC-3’	5’-CGCTGCTGCTAATGGCCGCGC-3’
879590	PA5545	Frameshift mutation	5’-CGTCGTAGGTGCCGGCGGGAA-3’	5’-CGTCGTAGGTGCGGCGGGAA-3’
880803	PA0690	Frameshift mutation	5’-CCGGCGAGGTCGGCGCGCTGG-3’	5’-CCGGCGAGGTCGCGCGCTGG-3’
881861	rpsC	Frameshift mutation	5’-GCAGGGGCACACGACCTTCGC-3’	5’-GCAGGGGCACAGACCTTCGC-3’
881508	PA4326	Frameshift mutation	5’-CTCCAGCCGCGCCTTGGCACG-3’	5’-CTCCAGCCGCGCTTGGCACG-3’
882154	PA0644	Frameshift mutation	5’-TGACAGGGAACGTCTCAGCGA-3’	5’-TGACAGGGAACTCTCAGCGA-3’
878727	hpaA	Frameshift mutation	5’-CGTCAGCGGCGCCAAGGTGGT-3’	5’-CGTCAGCGGCGCAAGGTGGT-3’
878660	PA5507	Frameshift mutation	5’-TGCCTGGAAGCGATCAAGGGC-3’	5’-CGTCAGCGGCGCAAGGTGGT-3’
878952	lipB	Frameshift mutation	5’-CCGGCTACGACGGCGACCGCG-3’	5’-CCGGCTACGACGCGACCGCG-3’
881415	PA4675	Frameshift mutation	5’-GCTGACGAAGTCGATCTGCTT-3’	5’-GCTGACGAAGTGATCTGCTT-3’
881340	PA4391	Frameshift mutation	5’-GCCGCCATCGACGATCCGCAC-3’	5’-GCCGCCATCGAGATCCGCAC-3’
881700	PA4746	Frameshift mutation	5’-CACGGAGAATGCCTTGGTAGT-3’	5’-CACGGAGAATGCTTGGTAGT-3’
880435	PA5475	Frameshift mutation	5’-GGTGGAACAGCGTACCTGGAA-3’	5’-GGTGGAACAGCTACCTGGAA-3’
882067	nadB	Frameshift mutation	5’-AGCCACTGGATCGCTTCGCGG-3’	5’-AGCCACTGGATGCTTCGCGG-3’
878522	PA4913	Frameshift mutation	5’-CTCGTCGTAGACCTCGGATGC-3’	5’-CTCGTCGTAGACTCGGATGC-3’

[1] #These authors contributed equally to this work. Correspondence to: Yiqiang Chen, Jinliang Kong E-mail: 2667455027@qq.com, 158514904@qq.com

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Differential Proteomic and Genomic Comparison of Resistance Mechanism of Pseudomonas aeruginosa to Cefoperazone Sodium/Sulbactam Sodium

Abstract