Medical‐Grade Honey Kills Antibiotic‐Resistant Bacteria In Vitro and Eradicates Skin Colonization

AbstractThe evolution of antibiotic resistant bacteria threatens to become the leading cause of worldwide mortality. This crisis has renewed interest in the practice of phage therapy. Yet, bacteria’s capacity to evolve resistance is likely to debilitate this therapy as well. To combat the evolution of phage resistance and improve treatment outcomes, many have suggested leveraging phages’ ability to counter resistance by evolving phages on target hosts before using them in therapy (phage training). We found that during in vitro experiments, a phage trained for 28 days suppressed bacteria ∼1000-fold for 3-8 times longer than its untrained ancestor. This extension was due to a delay in the evolution of resistance. Several factors contributed to this prolonged suppression. Mutations that confer resistance to trained phages are ∼100× less common and, while the target bacterium can evolve complete resistance to the untrained phage in a single step, multiple mutations are required to evolve complete resistance to trained phages. Mutations that confer resistance to trained phages are more costly than mutations for untrained phage resistance. And when resistance does evolve, trained phages are better able to suppress these forms of resistance. One way the trained phage improved was through recombination with a gene in a defunct prophage in the host genome, which doubled phage fitness. This direct transfer of information encoded by the host but originating from a relict phage provides a previously unconsidered mode of training phage. Overall, we provide a case study for successful phage training and uncover mechanisms underlying its efficacy.Significance StatementThe evolution of antibiotic resistant bacteria threatens to claim over 10 million lives annually by 2050. This crisis has renewed interest in phage therapy, the use of bacterial viruses to treat infections. A major barrier to successful phage therapy is that bacteria readily evolve phage resistance. One idea proposed to combat resistance is “training” phages by using their natural capacity to evolve to counter resistance. Here, we show that training phages by coevolving them with their host for one month enhanced their capacity for suppressing bacterial growth and delayed the emergence of resistance. Enhanced suppression was caused by several mechanisms, suggesting that the coevolutionary training protocol produces a robust therapeutic that employs complementary modes of action.

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ANTIBIOTIC THERAPY

PEDIATRICS ◽

10.1542/peds.20.2.362 ◽

1957 ◽

Vol 20 (2) ◽

pp. 362-365

Author(s):

Erwin Neter ◽

Horace L. Hodes

Keyword(s):

Bacterial Species ◽

Resistant Bacteria ◽

Antibiotic Resistant Bacteria ◽

Antibiotic Resistant ◽

Group A ◽

Laboratory Examinations ◽

Hospital Acquired ◽

Etiologic Diagnosis

THE LIBERAL, though not indiscriminate, use of antibiotics in pediatrics has resulted in far more assets than liabilities, although the statement has been made that 90% of antibiotics used in this country today are wasted. Often the pediatrician is able to select the correct and most effective antibiotic on the basis of clinical examination alone. At other times, laboratory examinations are necessary to establish an etiologic diagnosis. This information frequently allows the selection of the most favorable antibiotic when the bacterial species is of predictable sensitivity. Cases in which the bacterial species isolated are of unpredictable sensitivity require determination of the in-vitro efficacy of antibiotics. It must be stressed that many bacterial pathogens are as sensitive to penicillin and other antibiotics today as they were years ago, and that the emergence of antibiotic-resistant bacteria is not a general phenomenon. For example, the vast majority of strains of group A hemolytic streptococcus, gonococcus, pneumococcus, influenza bacillus, and the spirochete of syphilis have not become antibiotic resistant. In contrast, the staphylococcus has become a serious problem, particularly in hospitals and hospital-acquired infections. With the widespread use of penicillin and other antibiotics the percentage of antibiotic-resistant bacteria isolated from lesions in man has increased substantially. In addition, workers in hospitals rather frequently have become carriers of these strains and thus may in turn spread the infection to patients. Status of Current Antibiotics During the last few years several antibiotics have been added to the armamentarium of the physician. The present status of these antibiotics or special preparations may be summed up as follows.

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Chlorhexidine Resistance in Antibiotic-Resistant Bacteria Isolated From the Surfaces of Dispensers of Soap Containing Chlorhexidine

Infection Control and Hospital Epidemiology ◽

10.1086/501996 ◽

2002 ◽

Vol 23 (11) ◽

pp. 692-695 ◽

Cited By ~ 56

Author(s):

Steven E. Brooks ◽

Mary A. Walczak ◽

Rizwanullah Hameed ◽

Patrick Coonan

Keyword(s):

Staphylococcus Aureus ◽

Bacterial Contamination ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Antibiotic Resistant Bacteria ◽

Antibiotic Resistant ◽

Gram Negative ◽

Methicillin Resistant

AbstractBacterial contamination with pan-resistant Acinetobacter and Klebsiella, multidrug-resistant Pseudomonas, and methicillin-resistant Staphylococcus aureus (MRSA) was noted on the surfaces of dispensers of hand soap with 2% chlorhexidine. Gram-negative isolates could multiply in the presence of 1% chlorhexidine. In contrast, MRSA was inhibited in vitro by chlorhexidine at concentrations as low as 0.0019%.

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Hypocrellin B-Mediated Photodynamic Inactivation of Gram-Positive Antibiotic-Resistant Bacteria: An In Vitro Study

Photobiomodulation Photomedicine and Laser Surgery ◽

10.1089/photob.2019.4656 ◽

2020 ◽

Vol 38 (1) ◽

pp. 36-42

Author(s):

Woodvine Otieno ◽

Chengcheng Liu ◽

Hong Deng ◽

Jiao Li ◽

Xiaoyan Zeng ◽

...

Keyword(s):

In Vitro Study ◽

Vitro Study ◽

Resistant Bacteria ◽

Photodynamic Inactivation ◽

Antibiotic Resistant Bacteria ◽

Gram Positive ◽

Antibiotic Resistant ◽

Hypocrellin B

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Bacteriophages Synergize with the Gut Microbial Community To CombatSalmonella

mSystems ◽

10.1128/msystems.00119-18 ◽

2018 ◽

Vol 3 (5) ◽

Cited By ~ 3

Author(s):

Yue O. O. Hu ◽

Luisa W. Hugerth ◽

Carina Bengtsson ◽

Arlisa Alisjahbana ◽

Maike Seifert ◽

...

Keyword(s):

Gut Microbiota ◽

Antibiotic Treatment ◽

Pathogenic Bacteria ◽

Resistant Bacteria ◽

Human Gut ◽

Antibiotic Resistant Bacteria ◽

Antibiotic Resistant ◽

Human Gut Microbiota ◽

Phage Treatment

ABSTRACTSalmonellainfection is one of the main causes of food-borne diarrheal diseases worldwide. Although mostSalmonellainfections can be cleared without treatment, some cause serious illnesses that require antibiotic treatment. In view of the growing emergence of antibiotic-resistantSalmonellastrains, novel treatments are increasingly required. Furthermore, there is a striking paucity of data on how a balanced human gut microbiota responds toSalmonellainfection. This study aimed to evaluate whether a balanced gut microbiota protects againstSalmonellagrowth and to compare two antimicrobial approaches for managingSalmonellainfection: bacteriophage (phage) treatment and antibiotic treatment. Anaerobically cultivated human intestinal microflora (ACHIM) is a feasible model for the human gut microbiota and naturally inhibitsSalmonellainfection. By mimickingSalmonellainfectionin vitrousing ACHIM, we observed a large reduction ofSalmonellagrowth by the ACHIM itself. Treatments with phage and antibiotic further inhibitedSalmonellagrowth. However, phage treatment had less impact on the nontargeted bacteria in ACHIM than the antibiotic treatment did. Phage treatment has high specificity when combatingSalmonellainfection and offers a noninvasive alternative to antibiotic treatment.IMPORTANCEAntibiotic-resistant bacteria are a global threat. Therefore, alternative approaches for combatting bacteria, especially antibiotic-resistant bacteria, are urgently needed. Using a human gut microbiota model, we demonstrate that bacteriophages (phages) are able to substantially decrease pathogenicSalmonellawithout perturbing the microbiota. Conversely, antibiotic treatment leads to the eradication of close to all commensal bacteria, leaving only antibiotic-resistant bacteria. An unbalanced microbiota has been linked to many diseases both in the gastrointestinal tract or “nonintestinal” diseases. In our study, we show that the microbiota provides a protective effect againstSalmonella. Since phage treatment preserves the healthy gut microbiota, it is a feasible superior alternative to antibiotic treatment. Furthermore, when combating infections caused by pathogenic bacteria, gut microbiota should be considered.

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Exogenous Citrulline and Glutamine Contribute to Reverse the Resistance of Salmonella to Apramycin

Frontiers in Microbiology ◽

10.3389/fmicb.2021.759170 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yan Yong ◽

Yanhong Zhou ◽

Kexin Liu ◽

Guochang Liu ◽

Liqin Wu ◽

...

Keyword(s):

Bacterial Resistance ◽

Tricarboxylic Acid Cycle ◽

Animal Health ◽

Resistant Bacteria ◽

Drug Resistant ◽

Bacterial Cells ◽

Antibiotic Resistant Bacteria ◽

Antibiotic Resistant ◽

Drug Resistant Bacteria

Antibiotic resistance is an increasing concern for human and animal health worldwide. Recently, the concept of reverting bacterial resistance by changing the metabolic state of antibiotic-resistant bacteria has emerged. In this study, we investigated the reversal of Apramycin resistance in Salmonella. First, non-targeted metabonomics were used to identify key differential metabolites of drug-resistant bacteria. Then, the reversal effect of exogenous substances was verified in vivo and in vitro. Finally, the underlying mechanism was studied. The results showed that the metabolites citrulline and glutamine were significantly reduced in Apramycin-resistant Salmonella. When citrulline and glutamine were added to the culture medium of drug-resistant Salmonella, the killing effect of Apramycin was restored markedly. Mechanistic studies showed that citrulline and glutamine promoted the Tricarboxylic acid cycle, produced more NADH in the bacteria, and increased the proton-motive force, thus promoting Apramycin entry into the bacterial cells, and killing the drug-resistant bacteria. This study provides a useful method to manage infections by antibiotic-resistant bacteria.

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