From the Southern Hemisphere: Research on Resistance, Antibiotics and Treatments

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (31 March 2019) | Viewed by 69695

Special Issue Editors


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Guest Editor
School of Optometry and Vision Science, University of New South Wales, Sydney, NSW 2052, Australia
Interests: development of antimicrobial surfaces; new antimicrobials; bacterial resistance mechanisms; new treatments for infections
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
School of Optometry and Vision Science, University of New South Wales, Sydney, NSW 2052, Australia
Interests: contact lens and anterior ocular surface; tear film and lipid layer; ocular infection; antibiotic resistance; novel antimicrobial agents to counter bacterial resistance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

With the rise in antimicrobial resistance worldwide, many of us have been investigating new ways of overcoming this problem and treating disease. These new technologies may take the form of repurposing antimicrobials, combining antimicrobials for synergy, synthesising new antimicrobials, using phages and parasitic bacteria, as well as understanding the spread of resistance. In this issue we want to highlight new research from the Southern Hemisphere in these, and related areas. Studies can be laboratory based, pre-clinical or clinical; human or animal based. Manuscripts are particularly welcomed in the following areas:

  1. New antimicrobials, including antibiotics, disinfectants, metals
  2. Synthesis of antimicrobials
  3. New methods of testing antimicrobial activity
  4. Phages and parasitic bacteria
  5. Synergism between different types of antimicrobials
  6. Design and testing of antimicrobial surfaces
  7. Epidemiology and spread of microbes and resistance traits

Dr. Mark Willcox
Dr. Debarun Dutta
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

  • Antimicrobial activity
  • Antimicrobial testing
  • Surface bound antimicrobials
  • Antimicrobial release
  • Antimicrobial synergy
  • Resistance genes

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Published Papers (11 papers)

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Research

Jump to: Review

8 pages, 354 KiB  
Article
Antibacterial Performance of Terpenoids from the Australian Plant Eremophila lucida
by Israt J. Biva, Chi P. Ndi, Susan J. Semple and Hans J. Griesser
Antibiotics 2019, 8(2), 63; https://doi.org/10.3390/antibiotics8020063 - 17 May 2019
Cited by 15 | Viewed by 3861
Abstract
Plants in the Australian genus Eremophila (Scrophulariaceae) have attracted considerable recent attention for their antimicrobial compounds, which possess a wide range of chemical structures. As they are typically associated with the oily-waxy resin layer covering leaves and green branchlets, and Eremophila lucida is [...] Read more.
Plants in the Australian genus Eremophila (Scrophulariaceae) have attracted considerable recent attention for their antimicrobial compounds, which possess a wide range of chemical structures. As they are typically associated with the oily-waxy resin layer covering leaves and green branchlets, and Eremophila lucida is prominent among the species containing a pronounced sticky resin layer, this species was considered of interest for assessing its antibacterial constituents. The n-hexane fraction of the crude acetone extract of the leaves exhibited antibacterial activity against Staphylococcus aureus. Isolation led to the known compounds cembratriene, (3Z, 7E, 11Z)-15-hydroxycembra-3,7,11-trien-19-oic acid (1), the sesquiterpenoid, farnesal (2) and the viscidane diterpenoid, 5α-hydroxyviscida-3,14-dien-20-oic acid (3). The purified compounds were tested for antibacterial activity with 2 and 3 showing moderate antibacterial activity against Gram-positive bacteria. Full article
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7 pages, 1053 KiB  
Article
A Pilot Study of the Synergy between Two Antimicrobial Peptides and Two Common Antibiotics
by Franziska Kampshoff, Mark D. P. Willcox and Debarun Dutta
Antibiotics 2019, 8(2), 60; https://doi.org/10.3390/antibiotics8020060 - 9 May 2019
Cited by 47 | Viewed by 7448
Abstract
Background: Frequent and unrestricted use of antibiotics has been associated with the development of antibiotic resistance by microorganisms. Thus, there is a need to find novel antibacterial agents or a combination of agents as the first line of treatment for various infections. This [...] Read more.
Background: Frequent and unrestricted use of antibiotics has been associated with the development of antibiotic resistance by microorganisms. Thus, there is a need to find novel antibacterial agents or a combination of agents as the first line of treatment for various infections. This study aimed to investigate the synergy between antimicrobial peptide (AMP) combinations or between AMP-antibiotics combinations using two common pathogens, Pseudomonas aeruginosa and Staphylococcus aureus. Methods: The AMPs melimine, Mel4 and protamine, and antibiotics cefepime and ciprofloxacin were used in this study. The minimum inhibitory concentration (MIC) of each were evaluated against P. aeruginosa and S. aureus strains by a microtiter broth dilution. Based on the MIC of each antimicrobial agent, a checkerboard assay was performed to investigate the synergy between them, which was expressed as the fractional inhibitory concentration (FIC). Results: The combination of melimine and ciprofloxacin showed synergistic activity against antibiotic sensitive or resistant strains of P. aeruginosa and with FIC values ≤0.5. Conclusion: Combinations of AMPs and the fluoroquinolone ciprofloxacin is a promising method for reducing resistance to the fluoroquinolone of P. aeruginosa. Full article
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9 pages, 832 KiB  
Article
Drug Susceptibility Testing and Synergistic Antibacterial Activity of Curcumin with Antibiotics against Enterotoxigenic Escherichia coli
by Rangel-Castañeda Itzia Azucena, Cruz-Lozano José Roberto, Zermeño-Ruiz Martin, Cortes-Zarate Rafael, Hernández-Hernández Leonardo, Tapia-Pastrana Gabriela and Castillo-Romero Araceli
Antibiotics 2019, 8(2), 43; https://doi.org/10.3390/antibiotics8020043 - 18 Apr 2019
Cited by 35 | Viewed by 5941
Abstract
Aim: This study investigated the susceptibility of Enterotoxigenic Escherichia coli to curcumin, as well as its synergistic effect with 12 antimicrobial drugs. Methods and Results: Our study shows that curcumin did not affect bacterial growth. The antimicrobial susceptibility of curcumin and antibiotic synergy [...] Read more.
Aim: This study investigated the susceptibility of Enterotoxigenic Escherichia coli to curcumin, as well as its synergistic effect with 12 antimicrobial drugs. Methods and Results: Our study shows that curcumin did not affect bacterial growth. The antimicrobial susceptibility of curcumin and antibiotic synergy were identified using disc diffusion on Mueller-Hinton agar. The strain of Enterotoxigenic Escherichia coli used was resistant to Ampicillin, Amoxicillin/Clavulanic acid, Ampicillin/Sulbactam, Ciprofloxacin, and Cefazolin. There was synergy between curcumin and the majority of antibiotics tested. Maximum synergy was observed with combinations of 330 µg/mL curcumin and Ceftazidime, followed by Cefotaxime, Amoxicillin/Clavulanic acid, Ampicillin, Aztreonam, Trimethoprim, Ciprofloxacin, Ceftriaxone, Cefazolin, Tetracycline, and Imipenem. Conclusion: Our findings indicated that curcumin might be useful as a combinatorial strategy to combat the antibiotic resistance of Enterotoxigenic Escherichia coli. Full article
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15 pages, 2300 KiB  
Article
Rifampicin-Loaded Mesoporous Silica Nanoparticles for the Treatment of Intracellular Infections
by Santhni Subramaniam, Nicky Thomas, Hanna Gustafsson, Manasi Jambhrunkar, Stephen P. Kidd and Clive A. Prestidge
Antibiotics 2019, 8(2), 39; https://doi.org/10.3390/antibiotics8020039 - 11 Apr 2019
Cited by 51 | Viewed by 7999
Abstract
Infectious diseases remain a major burden in today’s world, causing high mortality rates and significant economic losses, with >9 million deaths per year predicted by 2030. Invasion of host cells by intracellular bacteria poses treatment challenges due to the poor permeation of antimicrobials [...] Read more.
Infectious diseases remain a major burden in today’s world, causing high mortality rates and significant economic losses, with >9 million deaths per year predicted by 2030. Invasion of host cells by intracellular bacteria poses treatment challenges due to the poor permeation of antimicrobials into the infected cells. To overcome these limitations, mesoporous silica nanoparticles (MSNP) loaded with the antibiotic rifampicin were investigated as a nanocarrier system for the treatment of intracellular bacterial infection with specific interest in the influence of particle size on treatment efficiency. An intracellular infection model was established using small colony variants (SCV) of S. aureus in macrophages to systemically evaluate the efficacy of rifampicin-loaded MSNP against the pathogen as compared to a rifampicin solution. As hypothesized, the superior uptake of MSNP by macrophages resulted in an enhanced treatment efficacy of the encapsulated rifampicin as compared to free antibiotic. This study provides a potential platform to improve the performance of currently available antibiotics against intracellular infections. Full article
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12 pages, 1196 KiB  
Article
Antifungal Activity in Compounds from the Australian Desert Plant Eremophila alternifolia with Potency Against Cryptococcus spp.
by Mohammed A. Hossain, Israt J. Biva, Sarah E. Kidd, Jason D. Whittle, Hans J. Griesser and Bryan R. Coad
Antibiotics 2019, 8(2), 34; https://doi.org/10.3390/antibiotics8020034 - 31 Mar 2019
Cited by 11 | Viewed by 5490
Abstract
Plant metabolites that have shown activity against bacteria and/or environmental fungi represent valuable leads for the identification and development of novel drugs against clinically important human pathogenic fungi. Plants from the genus Eremophila were highly valued in traditional Australian Aboriginal medicinal practices, and [...] Read more.
Plant metabolites that have shown activity against bacteria and/or environmental fungi represent valuable leads for the identification and development of novel drugs against clinically important human pathogenic fungi. Plants from the genus Eremophila were highly valued in traditional Australian Aboriginal medicinal practices, and E. alternifolia was the most prized among them. As antibacterial activity of extracts from E. alternifolia has been documented, this study addresses the question whether there is also activity against infectious fungal human pathogens. Compounds from leaf-extracts were purified and identified by 1- and 2-D NMR. These were then tested by disk diffusion and broth microdilution assays against ten clinically and environmentally relevant yeast and mould species. The most potent activity was observed with the diterpene compound, 8,19-dihydroxyserrulat-14-ene against Cryptococcus gattii and Cryptococcus neoformans, with minimum inhibition concentrations (MIC) comparable to those of Amphotericin B. This compound also exhibited activity against six Candida species. Combined with previous studies showing an antibacterial effect, this finding could explain a broad antimicrobial effect from Eremophila extracts in their traditional medicinal usage. The discovery of potent antifungal compounds from Eremophila extracts is a promising development in the search for desperately needed antifungal compounds particularly for Cryptococcus infections. Full article
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7 pages, 502 KiB  
Article
Chemical Profile, Antibacterial Activity and Antibiotic-Modulating Effect of the Hexanic Zea Mays L. Silk Extract (Poaceae)
by Ana Beatriz Linard de Carvalho, Cleciana Alves Cruz, Cicero Lucas Almeida de Freitas, José Junior dos Santos Aguiar, Paula Leticia Wendy de Souza Nunes, Valéria Maria da Silva Lima, Edinardo Fagner Ferreira Matias, Débora Feitosa Muniz and Henrique Douglas Melo Coutinho
Antibiotics 2019, 8(1), 22; https://doi.org/10.3390/antibiotics8010022 - 12 Mar 2019
Cited by 10 | Viewed by 4205
Abstract
The present study aimed to determine the chemical profile and to evaluate the antibacterial activity and antibiotic-modulating action of the hexanic Zea mays silk extract in association with aminoglycosides. Standard Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853 [...] Read more.
The present study aimed to determine the chemical profile and to evaluate the antibacterial activity and antibiotic-modulating action of the hexanic Zea mays silk extract in association with aminoglycosides. Standard Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853 strains, as well as multi-resistant Escherichia coli 27, Staphylococcus aureus 35, and Pseudomonas aeruginosa 31 strains, were used in this study. Phytochemical prospection revealed the presence of the following secondary metabolites: tannins, flavones, flavonoids, and xanthones, with the main chemical constituents being identified in plant extracts obtained with apolar organic solvents such as hexane. The extract presented a minimum inhibitory concentration (MIC) ≥1024 μg/mL against all the tested strains. The association of the extract with aminoglycoside antibiotics showed significant synergistic effects against Staphylococcus aureus and Pseudomonas aeruginosa, except for amikacin, which was antagonized by the extract against E. coli. These results indicate the Zea mays silk presents bioactive compounds with antibiotic-modulating properties. However, further research is required to characterize the effects of isolated compounds and determine their potential for drug development. Full article
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18 pages, 1834 KiB  
Article
Profluorescent Fluoroquinolone-Nitroxides for Investigating Antibiotic–Bacterial Interactions
by Anthony D. Verderosa, Rabeb Dhouib, Kathryn E. Fairfull-Smith and Makrina Totsika
Antibiotics 2019, 8(1), 19; https://doi.org/10.3390/antibiotics8010019 - 4 Mar 2019
Cited by 10 | Viewed by 5675
Abstract
Fluorescent probes are widely used for imaging and measuring dynamic processes in living cells. Fluorescent antibiotics are valuable tools for examining antibiotic–bacterial interactions, antimicrobial resistance and elucidating antibiotic modes of action. Profluorescent nitroxides are ‘switch on’ fluorescent probes used to visualize and monitor [...] Read more.
Fluorescent probes are widely used for imaging and measuring dynamic processes in living cells. Fluorescent antibiotics are valuable tools for examining antibiotic–bacterial interactions, antimicrobial resistance and elucidating antibiotic modes of action. Profluorescent nitroxides are ‘switch on’ fluorescent probes used to visualize and monitor intracellular free radical and redox processes in biological systems. Here, we have combined the inherent fluorescent and antimicrobial properties of the fluoroquinolone core structure with the fluorescence suppression capabilities of a nitroxide to produce the first example of a profluorescent fluoroquinolone-nitroxide probe. Fluoroquinolone-nitroxide (FN) 14 exhibited significant suppression of fluorescence (>36-fold), which could be restored via radical trapping (fluoroquinolone-methoxyamine 17) or reduction to the corresponding hydroxylamine 20. Importantly, FN 14 was able to enter both Gram-positive and Gram-negative bacterial cells, emitted a measurable fluorescence signal upon cell entry (switch on), and retained antibacterial activity. In conclusion, profluorescent nitroxide antibiotics offer a new powerful tool for visualizing antibiotic–bacterial interactions and researching intracellular chemical processes. Full article
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7 pages, 224 KiB  
Article
Study of Disinfectant Resistance Genes in Ocular Isolates of Pseudomonas aeruginosa
by Dinesh Subedi, Ajay Kumar Vijay and Mark Willcox
Antibiotics 2018, 7(4), 88; https://doi.org/10.3390/antibiotics7040088 - 15 Oct 2018
Cited by 14 | Viewed by 5142
Abstract
Background: The prevalence of disinfectant resistance in Pseudomonas aeruginosa is on the rise. P. aeruginosa is the most common bacteria isolated from cases of microbial keratitis. Many multi-purpose contact lens disinfectant solutions are available to decontaminate contact lenses before use and to help [...] Read more.
Background: The prevalence of disinfectant resistance in Pseudomonas aeruginosa is on the rise. P. aeruginosa is the most common bacteria isolated from cases of microbial keratitis. Many multi-purpose contact lens disinfectant solutions are available to decontaminate contact lenses before use and to help reduce the incidence of infections. However, with increasing disinfectant resistance, the effect of multi-purpose disinfectant solutions may diminish. The goal of this study was to examine genes associated with disinfectant resistance in ocular isolates of P. aeruginosa and understand the strain’s susceptibility to different multipurpose disinfectant solutions. Methods: Seven potential disinfectant resistance genes were used in BLASTn searches against the whole genomes of 13 eye isolates of P. aeruginosa. A microdilution broth method was used to examine susceptibility to four different multipurpose disinfectant solutions. Results: All strains possessed the sugE2, sugE3 and emrE (qacE) genes. The sugE1 and qacEdelta1 genes were present in 6/13 isolates. No strains contained the qacF or qacG genes. All tested disinfectant solutions had the ability to kill all test strains at 100% concentration, with some strains being susceptible at 1:8 dilutions of the disinfecting solutions. However, the presence of disinfectant resistance genes was not associated with susceptibility to multi-purpose disinfectants. Conclusion: All four tested contact lens disinfectant preparations are effective against P. aeruginosa isolates regardless of the presence of disinfectant resistance genes. Full article

Review

Jump to: Research

23 pages, 406 KiB  
Review
The Case for a More Holistic Approach to Dry Eye Disease: Is It Time to Move beyond Antibiotics?
by Azadeh Tavakoli and Judith Louise Flanagan
Antibiotics 2019, 8(3), 88; https://doi.org/10.3390/antibiotics8030088 - 30 Jun 2019
Cited by 15 | Viewed by 8485
Abstract
Dry eye disease (DED) is one of the most frequent presentations to optometrists with over 16 million US adults (6.8% of adult population) diagnosed as having this disorder. The majority of associated marketed products offer relief from symptomatology but do not address aetiology. [...] Read more.
Dry eye disease (DED) is one of the most frequent presentations to optometrists with over 16 million US adults (6.8% of adult population) diagnosed as having this disorder. The majority of associated marketed products offer relief from symptomatology but do not address aetiology. DED harbours many distinguishing features of a chronic inflammatory disorder. The recent explosion in human microbiome research has sparked interest in the ocular microbiome and its role in the preservation and extension of ocular surface health and in the contribution of the gut microbiome to chronic systemic inflammation and associated “Western life-style” diseases. With a significant lack of success for many patients using currently available DED treatments, in this era of the microbiome, we are interested in exploring potential novel therapies that aim to reconstitute healthy bacterial communities both locally and distally (in the gut) as a treatment for DED. Although this direction of investigation is in its infancy, burgeoning interest makes such a review timely. This paper considers a number of studies into the use functional foods and associated products to ameliorate dry eye. Full article
31 pages, 12994 KiB  
Review
Short Cationic Peptidomimetic Antimicrobials
by Rajesh Kuppusamy, Mark Willcox, David StC. Black and Naresh Kumar
Antibiotics 2019, 8(2), 44; https://doi.org/10.3390/antibiotics8020044 - 18 Apr 2019
Cited by 51 | Viewed by 8021
Abstract
The rapid growth of antimicrobial resistance against several frontline antibiotics has encouraged scientists worldwide to develop new alternatives with unique mechanisms of action. Antimicrobial peptides (AMPs) have attracted considerable interest due to their rapid killing and broad-spectrum activity. Peptidomimetics overcome some of the [...] Read more.
The rapid growth of antimicrobial resistance against several frontline antibiotics has encouraged scientists worldwide to develop new alternatives with unique mechanisms of action. Antimicrobial peptides (AMPs) have attracted considerable interest due to their rapid killing and broad-spectrum activity. Peptidomimetics overcome some of the obstacles of AMPs such as high cost of synthesis, short half-life in vivo due to their susceptibility to proteolytic degradation, and issues with toxicity. This review will examine the development of short cationic peptidomimetics as antimicrobials. Full article
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13 pages, 2984 KiB  
Review
The Use of Tethered Bilayer Lipid Membranes to Identify the Mechanisms of Antimicrobial Peptide Interactions with Lipid Bilayers
by Amani Alghalayini, Alvaro Garcia, Thomas Berry and Charles G. Cranfield
Antibiotics 2019, 8(1), 12; https://doi.org/10.3390/antibiotics8010012 - 30 Jan 2019
Cited by 47 | Viewed by 6605
Abstract
This review identifies the ways in which tethered bilayer lipid membranes (tBLMs) can be used for the identification of the actions of antimicrobials against lipid bilayers. Much of the new research in this area has originated, or included researchers from, the southern hemisphere, [...] Read more.
This review identifies the ways in which tethered bilayer lipid membranes (tBLMs) can be used for the identification of the actions of antimicrobials against lipid bilayers. Much of the new research in this area has originated, or included researchers from, the southern hemisphere, Australia and New Zealand in particular. More and more, tBLMs are replacing liposome release assays, black lipid membranes and patch-clamp electrophysiological techniques because they use fewer reagents, are able to obtain results far more quickly and can provide a uniformity of responses with fewer artefacts. In this work, we describe how tBLM technology can and has been used to identify the actions of numerous antimicrobial agents. Full article
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