Iodine-antibiotic mix shows promise to treat bacterial infections

A new drug containing iodine can help to kill versions of the diarrhoea-causing bacteria Escherichia coli (E.coli) that have otherwise become resistant to standard antibiotic treatment.   

Many disease-causing bacteria have over time adapted and changed their structure or genetics. In doing so, they have become resistant to (unaffected by) the types of antibiotics that are typically used to kill them.   

Such so-called antibiotic resistance is increasing. Doctors and health professionals are worried that infections will soon be as widespread, uncontrolled, and untreatable as they were in the days before antibiotics.

Researchers are therefore working hard to find and test new methods and medicines.

Some have turned to iodine, a mineral that occurs naturally in seawater and some soils, salts and plants. It was one of the first medicines ever used against bacteria. It has been used since 1811.

Iodine is a good option to investigate, because so far no one has yet found a bacterium that is resistant to it.

A new drug containing iodine, called FS-1, was previously developed. Other researchers are now continuing this work. They study which resistant versions of bacteria can be killed when it is used together with standard antibiotics.

In the current study, researchers from Kazakhstan and South Africa tested whether such a mixture of medicines helps to kill the resistant versions of E.coli. They also studied what happens inside the cell and with its genetic structure in the process.

Studying E.coli is worthwhile. People who eat food or drink water containing it can suffer severe diarrhoea, stomach pain and cramps. Children who are not treated fast enough can die because of it.

Health officials are worrying because resistant versions of E.coli are spreading worldwide. Many infections are becoming untreatable.

The research team treated resistant E.coli cells for 30 minutes with a mixture of FS-1 and antibiotics called amoxicillin, ampicillin and piperacillin. They also treated similar cells without adding FS-1 as a control (part of the experiment that is not exposed to the condition being studied so that researchers can compare the effect with and without FS-1).

They then used advanced technology to look into the cells and to see what effect the treatments had.

They found that antibiotics mixed with FS-1 are better able to kill resistant versions of E.coli. This mixture changes the structure and functioning of resistant E.coli cells. It becomes unable to withstand antibiotic treatment.

Previous studies showed that FS-1, in combination with antibiotics, also kills the resistant versions of the bacteria that cause tuberculosis (Mycobacterium tuberculosis) and severe throat and skin infections (Staphylococcus aureus).

The researchers are hopeful that FS-1, in combination with antibiotics, will work against other types of antibiotic resistant infections too. Such untreatable infections are increasingly occurring in hospitals in Africa and elsewhere.

Abstract

Background Recent studies showed promising results on application of iodine-containing nanomicelles, FS-1, against antibiotic resistant pathogens. The effect was studied on Escherichia coli ATCC BAA-196.

Materials & methods RNA sequencing for transcriptomics and the complete genome sequencing by SMRT PacBio RS II technology followed by genome assembly and methylomics study were performed.

Results & conclusions FS-1 treated E. coli showed an increased susceptibility to antibiotics ampicillin and gentamicin. The analysis of differential gene regulation showed that possible targets of iodine-containing particles are cell membrane fatty acids and proteins, particularly cytochromes, that leads to oxidative, osmotic and acidic stresses. Cultivation with FS-1 caused gene expression alterations towards anaerobic respiration, increased anabolism and inhibition of many nutrient uptake systems. Identification of methylated nucleotides showed an altered pattern in the FS-1 treated culture. Possible role of transcriptional and epigenetic modifications in the observed increase in susceptibility to gentamicin and ampicillin were discussed.

Lay abstract New approaches of combatting drug resistance infections are in demand as the development of new antibiotics is in a deep crisis. This study was set out to investigate molecular mechanisms of action of new iodine-containing nano-micelle drug FS-1, which potentially may improve the antibiotic therapy of drug resistant infections. Iodine is one of the oldest antimicrobials and until now there were no reports on development of resistance to iodine. Recent studies showed promising results on application of iodine-containing nano-micelles against antibiotic resistant pathogens as a supplement to antibiotic therapy. The mechanisms of action, however, remain unclear. The collection strain Escherichia coli ATCC BAA-196 showing an extended spectrum of resistance to beta-lactam and aminoglycoside antibiotics was used in this study as a model organism. Antibiotic resistance patterns, whole genomes and total RNA sequences of the FS-1 treated (FS) and negative control (NC) variants of E. coli BAA-196 were obtained and analyzed. FS culture showed an increased susceptibility to antibiotics associated with profound gene expression alterations switching the bacterial metabolism to anaerobic respiration, increased anabolism, osmotic stress response and inhibition of many nutrient uptake systems. Nucleotide methylation pattern were identified in FS and NC cultures. While the numbers of methylated sites in both genomes remained similar, some peculiar alterations were observed in their distribution along chromosomal and plasmid sequences.

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