Ciprofloxacin

• “What doesn’t kill me makes me stronger”, originally coined by Friedrich Nietzsche in 1888, is a perfect description of how bacteria develop antibiotic resistance.
• Contrary to a common belief, antibiotic resistance is not about your body becoming resistant to antibiotics.

How bacteria adapt

• The ability for bacteria to adapt lies in part with their astonishing rate of reproduction.
• While most changes are bad, sometimes they can help the bacteria grow in the presence of an antibiotic.
• This evolution of resistance can be seen by growing bacteria on a large agar plate (a nutrient support that bacteria like to grow on) with zones of increasing antibiotic levels.

They also exchange genetic material

• The other key mechanism enabling bacterial resistance is the exchange of genetic information between bacteria.
• In addition to the main chunk of DNA that encodes the bacterial genome, bacteria can host circular DNA snippets called plasmids.
• Plasmid exchange usually occurs by direct physical contact between bacteria.

4 ways bacteria resist

• Gram-positive bacteria like Staphylococcus aureus have a thick cell wall enclosing a lipid membrane.
• Antibiotics can hijack these entry routes, but bacteria can modify the cell wall, cell membrane and entry proteins to block antibiotic penetration.
• For example, bacteria increase the thickness of the cell wall to resist antibiotics like vancomycin.

• Bacteria have machinery known as efflux pumps, which regurgitate unwanted molecules from within the bacteria.
• Bacteria can alter the pump so it is more effective at removing the antibiotic, or they can simply make more pumps.
• Antibiotics, like most other drugs, generally work by blocking the function of important enzymes within the bacteria.
• If bacteria alter the target shape by changing the DNA/protein sequence, the antibiotic (key) can no longer bind to its target (lock).

Bacteria vs antibiotics

• While bacteria have developed mechanisms to resist antibiotics, these adaptations can come at a “fitness” cost.
• Bacteria may grow more slowly, or can be killed more easily by another antibiotic.
• This has led to the concept of “collateral sensitivity” to prevent or overcome resistance when treating patients, by using pairs of antibiotics.

Mark Blaskovich receives funding from a range of government, not-for-profit and commercial organisations for research into antibiotic discovery and development. He is affiliated with AAMRNet (Australian Antimicrobial Resistance Network), an organisation promoting improved care and development of antibiotics and antibiotic alternatives.

• But our new research shows that wild foods concentrate antibiotic-resistant bacteria and could put people at risk.
• But there are no guidelines for people who harvest wild foods to inform them about the risk of antibiotic resistance.
• Antibiotic-resistant bacteria make gastrointestinal infections from eating wild foods or contact infections acquired during harvest or food preparation more difficult, even impossible, to treat.

The creeping pandemic of antibiotic resistance

• Antibiotic resistance is one of the biggest threats to global health and food security, according to the World Health Organization.
• This process is happening in all bacteria, pathogenic or benign, leading to super strains that are resistant to multiple antibiotics.
• Because of the way antibiotic resistance genes clump together, super strains are usually super spreaders of antibiotic resistance.

E. coli on watercress and in mussels and cockles

• E. coli is used as an indicator for infection risk in water and food.
• In the sites we studied, concentrations of E. coli were consistently high over many years.
• We identified E. coli on plants (watercress) and in animals (mussels and cockles) taken for kai.
• In some samples, up to 20% of the E. coli were resistant to the frontline antibiotic drug ampicillin.

Safe to touch does not equal safe to eat

• Bacteria extracted from cockles were “ingested” during high tide and showed us what the water was like over that time period.
• In contrast, water samples, such as those used to inform swimming guidelines, represent only the conditions at the time of sampling.
• Our work shows that swimming guidance does not substitute for making decisions about whether or not to harvest wild kai.
• Jack Heinemann has received funding from Brian Mason Trust, Marsden Fund, and various other government, civil society, philanthropic, and industry sources.

• DUBLIN, Ireland and CHICAGO, May 12, 2023 (GLOBE NEWSWIRE) -- Iterum Therapeutics plc (Nasdaq: ITRM) (Iterum), a clinical-stage pharmaceutical company focused on developing next generation oral and IV antibiotics to treat infections caused by multi-drug resistant pathogens in both community and hospital settings, today reported financial results for the first quarter ended March 31, 2023.
• Research and development (R&D) expenses for the first quarter 2023 were $6.4 million, compared to $3.4 million for the same period in 2022.
• General and administrative (G&A) expenses for the first quarter 2023 were $2.1 million, compared to $3.9 million for the same period in 2022.
• Non-GAAP1 net loss for the first quarter 2023 of $7.4 million, compared to a non-GAAP1 net loss of $5.6 million for the same period in 2022.

• The synergistic mode of action of PrimeC as a combination therapy in ALS was measured in ALS-related biomarkers in neuronal derived exosomes (NDEs).
• Significant differences in ALS-related biomarkers were detected in people with ALS when compared to controls.
• PrimeC is currently being evaluated for the treatment of ALS in a Phase 2b study.
• A Phase 2 double-blind proof-of-concept AD study is expected to commence in H1 2023.