The research aim was to develop alternatives to antibiotics to prevent bacterial infection of cow udders.
Known as bovine mastitis, this infliction not only reduces milk production but raises health and safety concerns about antibiotic contamination and antimicrobial resistance (AMR).
It was led by Nanyang Technological University of Singapore (NTU), in collaboration with the Antimicrobial Resistance (AMR) Interdisciplinary Research Group at the Singapore-MIT Alliance for Research and Technology (SMART), Massachusetts Institute of Technology’s (MIT) research enterprise in Singapore.
In a preliminary farm trial, the new antimicrobial compounds were applied on cow teats and shown to stave off udder infection after the animals were exposed to bacteria.
“Our study has unveiled an alternative class of potent antimicrobial compounds that could be used in the agriculture industry to combat multi-drug-resistant bacteria that cause bovine mastitis,” said Professor Mary Chan from NTU’s School of Chemistry, Chemical Engineering and Biotechnology, and the Lee Kong Chian School of Medicine.
Professor Chan is also a principal investigator at the AMR Interdisciplinary Research Group at SMART.
The findings were published in the scientific journal Nature Communications.
Charge-shifting compounds
The main compounds at work are oligoimidazolium carbon acids (OIMs) which were initially developed as alternatives to fight antibiotic-resistant bacteria.
Speaking to AgTechNavigator, Chan explained how OIMs worked differently from their conventional counterparts.
“OIMs usually have a positive charge but can momentarily ‘switch off’ their charge. This happens when the OIMs’ unique chemical groups, called carbon acids, temporarily form neutral hydrophobic structures called carbenes under certain conditions similar to that in the body. When the OIMs’ positive charge is “off”, they can then slip through bacterial membranes without rupturing them.”
Once inside, the compounds revert back to their positively charged state to actively interact with and disrupt vital intracellular functions and molecules, such as DNA.
“This then leads to rapid death of the bacteria. Because the OIMs penetrate efficiently and can attack multiple targets in the bacteria, they kill bacteria at much lower doses than conventional antimicrobials,” said Chan.
On the other hand, with conventional solutions, higher doses are needed.
“Traditional antiseptics and antimicrobial polymers, like quaternary ammonium compounds and others that are positively charged, mainly work by rupturing bacterial membranes. That approach requires enough compound molecules to be accumulated at the bacteria’s membrane to reach a critical concentration before the membrane is damaged. This often requires higher doses to kill the bacteria, which limits how safe they can be,” said Chan.
New gear in the toolbox
This could be new strategy to overcome disease, even multi-drug-resistant bacteria, potentially transforming how scientist design antimicrobials to combat a major global problem – AMR.
“This discovery opens up a new paradigm to design antimicrobials. Instead of focusing on traditional compounds that act on the surface of bacteria and disrupt their membranes, we now know that dynamic chemical switching – the ability for molecules to temporarily switch off or change their charge – can be exploited to allow antimicrobials to cross bacteria membranes efficiently,” said Chan.
She elaborated that future antimicrobials could be designed to reach previously inaccessible targets within bacterial cells, particularly those that were resistant to positively charged compounds.
It could also enable these agents to maintain their potency at lower, safer concentrations.
Beyond medical applications, the findings may expand the use of antimicrobials to areas such as agriculture and food safety, reducing concerns about toxicity and harmful residues.
Moving forward, the team will move from proof-of-concept to “large-scale field validation and formulation optimisation.
It is currently running large farm trials in Malaysia to confirm long-term efficacy and stability of the OIMs under real farm conditions.
At the same time, the team will look to better under how the structure of the new antimicrobial compounds can affect their activity.
“Such as by tweaking the design of the compounds to balance their antimicrobial potency, biodegradability, cost-effectiveness and safety,” said Chan.
This innovation has already attracted strong interest from several agricultural companies across the global, including Australia, Belgium, Malaysia and New Zealand.
The team is keen to explore collaboration for commercial applications with corporate partners.
However, a few challenges remain, including regulatory approval and industry adoption.
“Even though our early farm and animal studies show good safety profiles, full regulatory approval requires more comprehensive assessments.
“Dairy farms have long used traditional disinfectants. Demonstrating consistent efficacy, user-friendliness, and milk safety will be critical to build confidence among farmers and regulators.”
Source: Nature Communications
Carbene formation as a mechanism for efficient intracellular uptake of cationic antimicrobial carbon acid polymers
Authors: Chan et al.
