The battle between antibiotics and bacteria is escalating, and the rise of superbs being resistant to our strongest drugs has attracted major attention. Interestingly, E. coli Many other bacteria adopt an interesting survival strategy when attacked by antibiotics: They slow down their division and extend into longer filament shapes. This strategy is not only a desperate measure, but also a peculiar way to avoid the body’s immune system and protect yourself with a shield-like layer. An unexpected discovery has been made in this microbial weapons competition. The introduction of Annexin A4, a protein that binds to certain fats in a calcium-dependent manner, can surprisingly restore the normal division process of bacteria even under the pressure of antibiotics. This unexpected assistant from the animal world brings a spark of hope to people, suggesting a new drug-resistant bacteria that makes them vulnerable to antibiotics and our bodies’ defenses again.
Figure 1. Production of bovine annexin A4 in coli bacteria restores cell division blocked by antibiotics. Left picture: Bacteria and cephalosporin incubated in the antibiotic ampicillin cannot divide as they grow, resulting in an elongated shape that is difficult to consume and destroy. Right: When the bacteria also produce bovine annexin A4, the cells can divide again, resulting in smaller bacteria, which can be “swallowed” and destroyed by white blood cells. (Photosed with a deep field optical microscope. The length of the white scale bar in each panel is equal to 50 microns).
A new way to fight antibiotic resistance has been revealed in the groundbreaking research of Professor Carl Creutz of the University of Virginia. The survey, published in the Biochemistry and Biophysics report, shows that bovine membrane agent A4 is added to E. coli The negative effects of beta-lactam antibiotics can be offset, which marks a major breakthrough in the battle against resistant bacterial strains.
Professor Creutz can share insights from the beginning of the study: “Introduction of a mammalian protein that binds to fat in a calcium-dependent manner, i.e. bovine membrane A4 A4 (i.e. E. coli) was found to counteract the effect of cell division on the cessation of cell division. . The antibiotics ampicillin, piperacillin and cephalomycin. “This discovery hints at a potential new strategy that can make bacteria more susceptible to antibiotic treatment and the body’s immune system, thus achieving normal bacterial division where antibiotics have stopped .
While exploring the methods used in the study, Professor Creutz turned to black field optical microscopy to track the development of bacterial filaments when exposed to antibiotics. As Professor Creutz explains, the technique “increases the visibility of bacteria in dark backgrounds, thus making it easier to change the shape of bacterial cell without often facing the complexity of traditional viewing methods.” This makes the study The person can see the effect of Annexin A4 on bacterial cells in real time, clearly demonstrating its role in reversing the fragmentation effect caused by antibiotics. In addition, Professor Cruz also used transmission electron microscopy to carefully study the structure of the cells, thus confirming what they saw on light microscopy at a more complex level. Together, these methods provide the effect of Annexin A4, linking visible changes in bacteria to the occurrence of deeper molecular effects.
In addition, Professor Cruz also used transmission electron microscopes to carefully observe the structure of the cells, thus confirming what they saw on the optical microscope at a more complex level. Together, these methods list the effects of Annexin A4, linking visible changes in bacteria to the occurrence of deeper molecular effects.
Figure 2: Electron microscopy of E. coli incubated with antibiotics shows detailed effects of calcium on the ability of annexin to promote cell division. Top left panel: Bacterial cells do not have any Annexin A4. A mixture of elongated and normal cells can be seen. Top right panel: Bacterial cells produce “normal” Annexin A4 with 4 calcium binding sites. Because Annexin causes certain cells to divide, fewer cell cells are seen. The lower left panel: Bacterial cells with only one very effective calcium binding site Annexin A4. Most cells shorten due to cell division. The right panel: Bacterial cells that produce Annexin A4 remove all calcium binding sites by mutation. More cells are elongated and “fat” because removing all calcium binding sites has reduced the ability of Annexin to promote cell division. (The length of the black mark bar is equal to 2.5 microns).
“Concerning the recovery of cell division is key to understanding how membrane toxin A4 affects bacterial cell division under antibiotic stress,” Professor Cruz noted. “Our findings suggest the importance of calcium binding to annexin and its attachment to membranes in It brings post-cell division aspects.”
The implications of this study are important, suggesting new ways to create other treatments to improve the effectiveness of current antibiotics. The University of Virginia has begun the process of patenting membrane toxins in antibacterial treatment, indicating the practical application potential of the discovery.
As the challenge of antibiotic resistance remains a global health issue, Professor Cruz’s research offers hope for more effective treatments. Future efforts will aim to confirm these results in organisms and have innovative therapeutic strategies that may lead to resistant bacterial infections.
Journal Reference
Carl Creutz, “Expression of Bovine Annexin A4 E. coli Rescue the bactericidality of cytokines blocked by β-LACTAM antibiotics “Biochemistry and Biophysics Report”, 2023. DOI: https://doi.org/10.1016/j.bbrep.2023.101553.
About the author
After earning a bachelor’s degree in physics from Stanford University (1969), a master’s degree in physics from the University of Wisconsin (1970). Dr. Creutz conducted basic research on molecular and cellular biology at NIH in Bethesda, Maryland at Biophysics (1976), at Johns Hopkins University (1976). He served as an employee researcher (1976-1979) and a senior staff researcher (1980-1981). In 1981, he was recruited to the University of Virginia as an assistant professor in the Department of Pharmacology. In 1987, he was promoted to associate professor and in 1994 he was promoted to full professor. In 2003, Dr. Cruz was elected as Harrison Professor of Pharmacology Teaching, where he also served as his professor of pharmacology.
