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Research article
JeongWoo Kang
Animal and Plant Quarantine Agency
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: The antibiotics generally used in farm animals are rapidly losing their effectiveness all over the world as bacteria develop antibiotic resistance. Like some other pathogenic bacteria multidrug-resistant strains of Salmonella enterica serovar Typhimurium (S. Typhimurium) are also frequently found in animals and humans which poses a major public health concern. New strategies are needed to block the development of resistance and to prolong the life of traditional antibiotics. Thus, this study aimed to increase the efficacy of existing antibiotics against S. Typhimurium by combining them with opportunistic phenolic compounds gallic acid (GA), epicatechin, epicatechin gallate, epigallocatechin and hamamelitannin. Fractional inhibitory concentration indexes (FICI) of phenolic compound-antibiotic combinations against S. Typhimurium were determined. Based on the FICI and clinical importance, 1 combination (GA and ceftiofur) was selected for evaluating its effects on the virulence factors of this bacterium. Viability of Rattus norvegicus (IEC-6) cell in presence of this antibacterial combination was evaluated.
Results: Minimum inhibitory concentrations (MICs) of GA, epigallocatechin and hamamelitannin found against different strains of S. Typhimurium were 256, (512–1024), and (512–1024) μg/mL, respectively. Synergistic antibacterial effect was obtained from the combination of erythromycin-epicatechin gallate (FICI: 0.50) against S. Typhimurium. Moreover, additive effects (FICI: 0.502–0.750) were obtained from 16 combinations against this bacterium. The time-kill assay and ultrastructural morphology showed that GA-ceftiofur combination more efficiently inhibited the growth of S. Typhimurium compared to individual antimicrobials. Biofilm viability, and swimming and swarming motilities of S. Typhimurium in presence of GA-ceftiofur combination were more competently inhibited than individual antimicrobials. Viabilities of IEC-6 cells were more significantly enhanced by GA-ceftiofur combinations than these antibacterials alone.
Conclusions: This study suggests that GA-ceftiofur combination can be potential medication to treat S. Typhimurium-associated diarrhea and prevent S. Typhimurium-associated blood-stream infections (e.g.: fever) in farm animals, and ultimately its transmission from animal to human. Further in vivo study to confirm these effects and safety profiles in farm animal should be undertaken for establishing these combinations as medications.
Keywords
Combination therapy, critically important antibiotics, phenolic compounds, gallic acid, hamamelitannin, biofilm
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View the published article at BMC Microbiology.
Version 6
Posted 11 May, 2020
No community comments so far
Editorial decision: Accept
On 01 May, 2020
Editor assigned
On 26 Apr, 2020
Submission checks complete
On 25 Apr, 2020
Editor invited
On 25 Apr, 2020
No comments provided
Editorial decision: Major revision
On 08 Apr, 2020
Review #2 received
Received 02 Apr, 2020
Review #1 received
Received 01 Apr, 2020
Reviewer #2 agreed
On 30 Mar, 2020
Reviewers invited
Invitations sent on 27 Mar, 2020
Reviewer #1 agreed
On 27 Mar, 2020
Editor assigned
On 17 Mar, 2020
Submission checks complete
On 16 Mar, 2020
Editor invited
On 16 Mar, 2020
No comments provided
Editorial decision: Major revision
On 18 Feb, 2020
Review #2 received
Received 15 Feb, 2020
Review #1 received
Received 07 Feb, 2020
Reviewer #2 agreed
On 31 Jan, 2020
Reviewers invited
Invitations sent on 28 Jan, 2020
Reviewer #1 agreed
On 28 Jan, 2020
Editor assigned
On 24 Jan, 2020
Submission checks complete
On 23 Jan, 2020
Editor invited
On 23 Jan, 2020
No comments provided
Review #2 received
Received 23 Dec, 2019
Editorial decision: Major revision
On 23 Dec, 2019
Reviewer #2 agreed
On 10 Dec, 2019
Review #1 received
Received 03 Dec, 2019
Reviewer #1 agreed
On 20 Nov, 2019
Reviewers invited
Invitations sent on 19 Nov, 2019
Editor assigned
On 13 Nov, 2019
Submission checks complete
On 12 Nov, 2019
Editor invited
On 12 Nov, 2019
No comments provided
Editorial decision: Major revision
On 14 Oct, 2019
Review #2 received
Received 29 Sep, 2019
Review #1 received
Received 23 Sep, 2019
Reviewer #2 agreed
On 13 Sep, 2019
Reviewers invited
Invitations sent on 12 Sep, 2019
Reviewer #1 agreed
On 12 Sep, 2019
Editor assigned
On 09 Sep, 2019
Submission checks complete
On 08 Sep, 2019
Editor invited
On 08 Sep, 2019
No comments provided
Editorial decision: Major revision
On 23 Jul, 2019
Review #1 received
Received 16 Jul, 2019
Review #2 received
Received 14 Jul, 2019
Reviewer #2 agreed
On 03 Jul, 2019
Reviewer #1 agreed
On 02 Jul, 2019
Reviewers invited
Invitations sent on 01 Jul, 2019
Submission checks complete
On 04 May, 2019
Editor invited
On 23 Apr, 2019
Editor assigned
On 23 Apr, 2019
First submitted
On 22 Apr, 2019
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See the published version of this preprint at BMC Microbiology.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
JeongWoo Kang
Animal and Plant Quarantine Agency
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Microbiology.
Version 6
Posted 11 May, 2020
No community comments so far
Editorial decision: Accept
On 01 May, 2020
Editor assigned
On 26 Apr, 2020
Submission checks complete
On 25 Apr, 2020
Editor invited
On 25 Apr, 2020
No comments provided
Editorial decision: Major revision
On 08 Apr, 2020
Review #2 received
Received 02 Apr, 2020
Review #1 received
Received 01 Apr, 2020
Reviewer #2 agreed
On 30 Mar, 2020
Reviewers invited
Invitations sent on 27 Mar, 2020
Reviewer #1 agreed
On 27 Mar, 2020
Editor assigned
On 17 Mar, 2020
Submission checks complete
On 16 Mar, 2020
Editor invited
On 16 Mar, 2020
No comments provided
Editorial decision: Major revision
On 18 Feb, 2020
Review #2 received
Received 15 Feb, 2020
Review #1 received
Received 07 Feb, 2020
Reviewer #2 agreed
On 31 Jan, 2020
Reviewers invited
Invitations sent on 28 Jan, 2020
Reviewer #1 agreed
On 28 Jan, 2020
Editor assigned
On 24 Jan, 2020
Submission checks complete
On 23 Jan, 2020
Editor invited
On 23 Jan, 2020
No comments provided
Review #2 received
Received 23 Dec, 2019
Editorial decision: Major revision
On 23 Dec, 2019
Reviewer #2 agreed
On 10 Dec, 2019
Review #1 received
Received 03 Dec, 2019
Reviewer #1 agreed
On 20 Nov, 2019
Reviewers invited
Invitations sent on 19 Nov, 2019
Editor assigned
On 13 Nov, 2019
Submission checks complete
On 12 Nov, 2019
Editor invited
On 12 Nov, 2019
No comments provided
Editorial decision: Major revision
On 14 Oct, 2019
Review #2 received
Received 29 Sep, 2019
Review #1 received
Received 23 Sep, 2019
Reviewer #2 agreed
On 13 Sep, 2019
Reviewers invited
Invitations sent on 12 Sep, 2019
Reviewer #1 agreed
On 12 Sep, 2019
Editor assigned
On 09 Sep, 2019
Submission checks complete
On 08 Sep, 2019
Editor invited
On 08 Sep, 2019
No comments provided
Editorial decision: Major revision
On 23 Jul, 2019
Review #1 received
Received 16 Jul, 2019
Review #2 received
Received 14 Jul, 2019
Reviewer #2 agreed
On 03 Jul, 2019
Reviewer #1 agreed
On 02 Jul, 2019
Reviewers invited
Invitations sent on 01 Jul, 2019
Submission checks complete
On 04 May, 2019
Editor invited
On 23 Apr, 2019
Editor assigned
On 23 Apr, 2019
First submitted
On 22 Apr, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Microbiology.
Background: The antibiotics generally used in farm animals are rapidly losing their effectiveness all over the world as bacteria develop antibiotic resistance. Like some other pathogenic bacteria multidrug-resistant strains of Salmonella enterica serovar Typhimurium (S. Typhimurium) are also frequently found in animals and humans which poses a major public health concern. New strategies are needed to block the development of resistance and to prolong the life of traditional antibiotics. Thus, this study aimed to increase the efficacy of existing antibiotics against S. Typhimurium by combining them with opportunistic phenolic compounds gallic acid (GA), epicatechin, epicatechin gallate, epigallocatechin and hamamelitannin. Fractional inhibitory concentration indexes (FICI) of phenolic compound-antibiotic combinations against S. Typhimurium were determined. Based on the FICI and clinical importance, 1 combination (GA and ceftiofur) was selected for evaluating its effects on the virulence factors of this bacterium. Viability of Rattus norvegicus (IEC-6) cell in presence of this antibacterial combination was evaluated.
Results: Minimum inhibitory concentrations (MICs) of GA, epigallocatechin and hamamelitannin found against different strains of S. Typhimurium were 256, (512–1024), and (512–1024) μg/mL, respectively. Synergistic antibacterial effect was obtained from the combination of erythromycin-epicatechin gallate (FICI: 0.50) against S. Typhimurium. Moreover, additive effects (FICI: 0.502–0.750) were obtained from 16 combinations against this bacterium. The time-kill assay and ultrastructural morphology showed that GA-ceftiofur combination more efficiently inhibited the growth of S. Typhimurium compared to individual antimicrobials. Biofilm viability, and swimming and swarming motilities of S. Typhimurium in presence of GA-ceftiofur combination were more competently inhibited than individual antimicrobials. Viabilities of IEC-6 cells were more significantly enhanced by GA-ceftiofur combinations than these antibacterials alone.
Conclusions: This study suggests that GA-ceftiofur combination can be potential medication to treat S. Typhimurium-associated diarrhea and prevent S. Typhimurium-associated blood-stream infections (e.g.: fever) in farm animals, and ultimately its transmission from animal to human. Further in vivo study to confirm these effects and safety profiles in farm animal should be undertaken for establishing these combinations as medications.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
This is a list of supplementary files associated with this preprint. Click to download.
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