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Research article
Md Akil Hossain
Animal and Plant Quarantine Agency
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7131-4814
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Bacteria have remarkable abilities to acquire resistance against antibiotics by several mechanisms. New strategies are needed to block the development of resistance and to prolong the life of traditional antibiotics. This study aimed to increase the efficacy of existing antibiotics by combining them with the opportunistic phenolic compound gallic acid (GA) and its derivatives. Fractional inhibitory concentration (FIC) indexes of phenolic compound-antibiotic combinations against Salmonella enterica serovar Typhimurium, Escherichia coli and Staphylococcus aureus were determined. Based on the FIC indexes and clinical importance, 3 combinations were selected to evaluate their effects on the virulence factors of these bacteria. The in vitro cytotoxicity of GA and hamamelitannin in the Rattus norvegicus (IEC-6) cell line were evaluated. Results: Phenolic compounds demonstrated considerable antibacterial effects as the minimum inhibitory concentrations (MICs) of epigallocatechin, GA and hamamelitannin found against different strains were (32–1024), (128–1024) and (512–≥2048) μg/mL, respectively. The FIC indexes of the combined antibacterials against these strains were 0.281–1.016. The ultrastructural morphology and time-kill assays showed that the GA-ceftiofur combination, and hamamelitannin-erythromycin and GA-ampicillin combinations more efficiently inhibited the growth of S. Typhimurium and E. coli, respectively, compared to the individual antibiotics. Biofilm viability and the swimming and swarming motilities of S. Typhimurium in the presence of GA-ceftiofur and E. coli in the presence of the hamamelitannin-erythromycin and GA-ampicillin combinations were more competently inhibited than individual antimicrobials. The 50% inhibitory concentrations (IC50) of GA and hamamelitannin in IEC-6 cells were 564.55 μM and 988.54 μM, respectively. Conclusions: The phenolic compounds increase the efficacy of existing antibiotics might be by disrupting virulence factors. We can conclude that these antibacterial combinations are safe and can be potential medications to treat S. Typhimurium, E. coli and S. aureus infections in animals and humans. Further study to confirm this effect in in vivo system and to determine the precise mechanism of action should be undertaken to establish these combinations as medications.
Keywords
Combination therapy, critically important antibiotics, Phenolic compounds, gallic acid, hamamelitannin, biofilm
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CURRENT STATUS: Published
View the published article at BMC Microbiology.
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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
Version 1
Posted 07 May, 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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Subject Areas
General Microbiology
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A new preprint design is coming!
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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
Md Akil Hossain
Animal and Plant Quarantine Agency
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7131-4814
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.
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
Version 1
Posted 07 May, 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: ...
Subject Areas
General Microbiology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Microbiology.
Background: Bacteria have remarkable abilities to acquire resistance against antibiotics by several mechanisms. New strategies are needed to block the development of resistance and to prolong the life of traditional antibiotics. This study aimed to increase the efficacy of existing antibiotics by combining them with the opportunistic phenolic compound gallic acid (GA) and its derivatives. Fractional inhibitory concentration (FIC) indexes of phenolic compound-antibiotic combinations against Salmonella enterica serovar Typhimurium, Escherichia coli and Staphylococcus aureus were determined. Based on the FIC indexes and clinical importance, 3 combinations were selected to evaluate their effects on the virulence factors of these bacteria. The in vitro cytotoxicity of GA and hamamelitannin in the Rattus norvegicus (IEC-6) cell line were evaluated. Results: Phenolic compounds demonstrated considerable antibacterial effects as the minimum inhibitory concentrations (MICs) of epigallocatechin, GA and hamamelitannin found against different strains were (32–1024), (128–1024) and (512–≥2048) μg/mL, respectively. The FIC indexes of the combined antibacterials against these strains were 0.281–1.016. The ultrastructural morphology and time-kill assays showed that the GA-ceftiofur combination, and hamamelitannin-erythromycin and GA-ampicillin combinations more efficiently inhibited the growth of S. Typhimurium and E. coli, respectively, compared to the individual antibiotics. Biofilm viability and the swimming and swarming motilities of S. Typhimurium in the presence of GA-ceftiofur and E. coli in the presence of the hamamelitannin-erythromycin and GA-ampicillin combinations were more competently inhibited than individual antimicrobials. The 50% inhibitory concentrations (IC50) of GA and hamamelitannin in IEC-6 cells were 564.55 μM and 988.54 μM, respectively. Conclusions: The phenolic compounds increase the efficacy of existing antibiotics might be by disrupting virulence factors. We can conclude that these antibacterial combinations are safe and can be potential medications to treat S. Typhimurium, E. coli and S. aureus infections in animals and humans. Further study to confirm this effect in in vivo system and to determine the precise mechanism of action should be undertaken to establish these combinations as medications.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
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