Augmented antibiotic resistance associated with cadmium induced alterations in Salmonella enterica serovar Typhi Original paper

What was studied?

This study explored the association between cadmium exposure and the development of antibiotic resistance in Salmonella enterica serovar Typhi, the pathogen responsible for typhoid fever. The researchers focused on how intracellular cadmium accumulation in clinical isolates of S. Typhi correlates with altered antibiotic resistance patterns. Through laboratory adaptation, the study demonstrated that cadmium exposure not only increased resistance to common antibiotics like ampicillin and ciprofloxacin but also induced phenotypic changes in the bacteria. These included alterations in growth responses, morphology, biofilm formation, and macrophage survival. The study also looked at the molecular mechanisms behind this resistance, such as changes in protein expression and the upregulation of metal-binding proteins.

Who was studied?

The study involved both a reference strain of S. Typhi (Ty2) and clinical isolates obtained from patients with typhoid fever. These clinical isolates were collected from different medical institutions in India. The bacteria were exposed to cadmium chloride (CdCl₂), and their response to cadmium was compared with their antibiotic susceptibility patterns. The isolates were adapted to sub-inhibitory concentrations of cadmium to assess the long-term effects of cadmium exposure. The research aimed to examine how cadmium-induced alterations influence the pathogen’s ability to resist antibiotics and survive under stressful conditions.

Most important findings

The study revealed that cadmium exposure led to a significant increase in the resistance of S. Typhi to multiple antibiotics. Clinical isolates that were initially sensitive to antibiotics became resistant after cadmium exposure, and resistant strains became even more resistant. The minimum inhibitory concentrations (MICs) for antibiotics such as ciprofloxacin and ampicillin increased substantially, with cadmium exposure correlating with higher levels of resistance. Exposure to cadmium resulted in changes to the pathogen’s growth patterns, including delayed growth in the lag phase and prolonged log phase.

Transmission electron microscopy revealed structural alterations in the bacteria, including a reduction in the periplasmic space and the appearance of electron-dense regions, indicating metal sequestration. Proteomic analysis identified significant changes in protein expression, including downregulation of porins, which are key components in the bacterial outer membrane that control the influx of antibiotics. The study also found that cadmium exposure led to increased biofilm formation and enhanced survival of S. Typhi within macrophages, indicating a higher capacity for persistence in the host.

Key implications

The findings underscore the worrying potential of heavy metal contamination in the environment to drive antibiotic resistance in pathogens like S. Typhi. The study highlights the role of environmental cadmium as a long-term selective pressure, co-selecting for both metal and antibiotic resistance in bacteria. This has major implications for public health, particularly in areas with high levels of environmental metal contamination. The increased biofilm formation and enhanced intracellular survival observed in cadmium-exposed S. Typhi suggest that these bacteria may be harder to treat and control in clinical settings. The results also point to the need for strategies to limit environmental exposure to heavy metals and to monitor the co-selection of metal and antibiotic resistance, which could help curb the rise of resistant infections.