Novel Inhibitors of Staphylococcus aureus Virulence Gene Expression and Biofilm Formation

ABSTRACT Carbon catabolite protein A (CcpA) is known to function as a major regulator of gene expression in different gram-positive organisms. Deletion of the ccpA homologue (saCOL1786) in Staphylococcus aureus was found to affect growth, glucose metabolization, and transcription of selected virulence determinants. In liquid culture, deletion of CcpA decreased the growth rate and yield; however, the effect was only transient during the exponential-growth phase as long as glucose was present in the medium. Depletion of glucose and production of lactate was delayed, while the level of excretion of acetate was less affected and was even higher in the mutant culture. On solid medium, in contrast, growth of the ΔccpA mutant resulted in smaller colonies containing a lower number of CFU per colony. Deletion of CcpA had an effect on the expression of important virulence factors of S. aureus by down-regulating RNAIII, the effector molecule of the agr locus, and altering the transcription patterns of hla, encoding α-hemolysin, and spa, encoding protein A. CcpA inactivation markedly reduced the oxacillin resistance levels in the highly methicillin-resistant S. aureus strain COLn and the teicoplanin resistance level in a glycopeptide-intermediate-resistant S. aureus strain. The presence of CcpA in the capsular polysaccharide serotype 5 (CP5)-producing strain Newman abolished capsule formation and decreased cap operon transcription in the presence of glucose. The staphylococcal CcpA thus not only is involved in the regulation of carbon metabolism but seems to function as a modulator of virulence gene expression as well.

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Association among biofilm formation, virulence gene expression, and antibiotic resistance in Proteus mirabilis isolates from diarrhetic animals in northeast China

10.21203/rs.2.16502/v2 ◽

2020 ◽

Author(s):

Yadong Sun ◽

Shanshan Wen ◽

Lili Zhao ◽

Qiqi Xia ◽

Yue Pan ◽

...

Keyword(s):

Gene Expression ◽

Antibiotic Resistance ◽

Biofilm Formation ◽

Northeast China ◽

Virulence Gene ◽

Drug Susceptibility ◽

Multidrug Resistant ◽

Virulence Gene Expression ◽

Biofilm Production ◽

High Level

Abstract Background The aim of this study was to investigate the association among biofilm formation, virulence gene expression, and antibiotic resistance in P. mirabilis isolates collected from diarrhetic animals (n = 176) in northeast China between September 2014 and October 2016. Results Approximately 92.05% of the isolates were biofilm producers, whereas 7.95% of the isolates were non-producers. The prevalence of virulence genes in biofilm producers was significantly higher than that in non-producers. Biofilm production was significantly associated with the expression of ureC , zapA , rsmA , hmpA , mrpA , atfA , and pmfA ( P < 0.05). Drug susceptibility tests revealed that approximately 76.7% of the isolates were multidrug-resistant (MDR) and extensively drug-resistant (XDR). Biofilm production was significantly associated with resistance to doxycycline, tetracycline, sulfamethoxazole, kanamycin, and cephalothin ( P < 0.05). Although the pathogenicity of the biofilm producers was stronger than that of the non-producers, the biofilm-forming ability of the isolates was not significantly associated with morbidity and mortality in mice ( P > 0.05). Conclusion Our findings suggested that a high level of multidrug resistance in diarrhetic animals infected with P. mirabilis in northeast China.The results of this study indicated that the positive rates of the genes expressed by biofilm-producing P. mirabilis isolates were significantly higher than those expressed by non-producing isolates.

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Nigribactin, a Novel Siderophore from Vibrio nigripulchritudo, Modulates Staphylococcus aureus Virulence Gene Expression

Marine Drugs ◽

10.3390/md10112584 ◽

2012 ◽

Vol 10 (12) ◽

pp. 2584-2595 ◽

Cited By ~ 15

Author(s):

Anita Nielsen ◽

Maria Mansson ◽

Matthias Wietz ◽

Anders Varming ◽

Richard Phipps ◽

...

Keyword(s):

Gene Expression ◽

Staphylococcus Aureus ◽

Virulence Gene ◽

Virulence Gene Expression

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Post-transcriptional control of virulence gene expression in Staphylococcus aureus

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms ◽

10.1016/j.bbagrm.2018.04.004 ◽

2019 ◽

Vol 1862 (7) ◽

pp. 734-741

Author(s):

Alexandre Le Scornet ◽

Peter Redder

Keyword(s):

Gene Expression ◽

Staphylococcus Aureus ◽

Transcriptional Control ◽

Virulence Gene ◽

Virulence Gene Expression

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Construction of a Multiplex Promoter Reporter Platform to Monitor Staphylococcus aureus Virulence Gene Expression and the Identification of Usnic Acid as a Potent Suppressor of psm Gene Expression

Frontiers in Microbiology ◽

10.3389/fmicb.2016.01344 ◽

2016 ◽

Vol 7 ◽

Cited By ~ 3

Author(s):

Peng Gao ◽

Yanli Wang ◽

Iván Villanueva ◽

Pak Leung Ho ◽

Julian Davies ◽

...

Keyword(s):

Gene Expression ◽

Staphylococcus Aureus ◽

Usnic Acid ◽

Virulence Gene ◽

Virulence Gene Expression

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Molecular Architecture of the Regulatory Locus sae of Staphylococcus aureus and Its Impact on Expression of Virulence Factors

Journal of Bacteriology ◽

10.1128/jb.185.21.6278-6286.2003 ◽

2003 ◽

Vol 185 (21) ◽

pp. 6278-6286 ◽

Cited By ~ 91

Author(s):

Andrea Steinhuber ◽

Christiane Goerke ◽

Manfred G. Bayer ◽

Gerd Döring ◽

Christiane Wolz

Keyword(s):

Gene Expression ◽

Staphylococcus Aureus ◽

Capsular Polysaccharide ◽

Virulence Gene ◽

Open Reading Frames ◽

Exponential Growth Phase ◽

Molecular Architecture ◽

Stem Loop ◽

Transcriptional Initiation ◽

Virulence Gene Expression

ABSTRACT We characterized the sae operon, a global regulator for virulence gene expression in Staphylococcus aureus. A Tn917 sae mutant was obtained by screening a Tn917 library of the agr mutant ISP479Mu for clones with altered hemolytic activity. Sequence analysis of the sae operon revealed two additional open reading frames (ORFs) (ORF3 and ORF4) upstream of the two-component regulatory genes saeR and saeS. Four overlapping sae-specific transcripts (T1 to T4) were detected by Northern blot analysis, and the transcriptional initiation points were mapped by primer extension analysis. The T1, T2, and T3 mRNAs are probably terminated at the same stem-loop sequence downstream of saeS. The T1 message (3.1 kb) initiates upstream of ORF4, T2 (2.4 kb) initiates upstream of ORF3, and T3 (2.0 kb) initiates in front of saeR. T4 (0.7 kb) represents a monocistronic mRNA encompassing ORF4 only. sae-specific transcripts were detectable in all of the 40 different clinical S. aureus isolates investigated. Transcript levels were at maximum during the post-exponential growth phase. The sae mutant showed a significantly reduced rate of invasion of human endothelial cells, consistent with diminished transcription and expression of fnbA. The expression of type 5 capsular polysaccharide is activated in the sae mutant of strain Newman, as shown by immunofluorescence and promoter-reporter fusion experiments. In summary, the sae operon constitutes a four-component regulator system which acts on virulence gene expression in S. aureus.

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18β-Glycyrrhetinic Acid Inhibits Methicillin-Resistant Staphylococcus aureus Survival and Attenuates Virulence Gene Expression

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01023-12 ◽

2012 ◽

Vol 57 (1) ◽

pp. 241-247 ◽

Cited By ~ 32

Author(s):

Danyelle R. Long ◽

Julia Mead ◽

Jay M. Hendricks ◽

Michele E. Hardy ◽

Jovanka M. Voyich

Keyword(s):

Gene Expression ◽

Staphylococcus Aureus ◽

Virulence Gene ◽

Glycyrrhetinic Acid ◽

Licorice Root ◽

Methicillin Resistant ◽

Content Type ◽

Virulence Gene Expression

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) has become a major source of infection in hospitals and in the community. Increasing antibiotic resistance inS. aureusstrains has created a need for alternative therapies to treat disease. A component of the licorice rootGlycyrrhizaspp., 18β-glycyrrhetinic acid (GRA), has been shown to have antiviral, antitumor, and antibacterial activity. This investigation explores thein vitroandin vivoeffects of GRA on MRSA pulsed-field gel electrophoresis (PFGE) type USA300. GRA exhibited bactericidal activity at concentrations exceeding 0.223 μM. Upon exposure ofS. aureusto sublytic concentrations of GRA, we observed a reduction in expression of key virulence genes, includingsaeRandhla. In murine models of skin and soft tissue infection, topical GRA treatment significantly reduced skin lesion size and decreased the expression ofsaeRandhlagenes. Our investigation demonstrates that at high concentrations GRA is bactericidal to MRSA and at sublethal doses it reduces virulence gene expression inS. aureusbothin vitroandin vivo.

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