tuberculosis bacteria growth study challenges theories

New Study Challenges Prevailing Theories on Tuberculosis Bacteria Growth

Introduction

Tuberculosis (TB), a rod-shaped bacterium ranked by the World Health Organization as the world's deadliest infectious disease, has been revealed as the first single-celled organism capable of maintaining a constant growth rate throughout its entire life cycle.

Groundbreaking Discovery

Researchers at Tufts University School of Medicine share this groundbreaking discovery in the journal Nature Microbiology on November 15, reshaping long-held views of bacterial cell biology and shedding light on the pathogen's resilience against immune defenses and antibiotics.

New Insights into TB Pathogen Behavior

"The study of bacterial growth and division is one of the simplest areas of research in microbiology, yet our findings show that the TB pathogen operates under an entirely unique set of principles." explained Bree Aldridge, co-senior author and professor at Tufts University School of Medicine and School of Engineering. Ariel Amir of the Weizmann Institute of Science also served as co-senior author.

Implications for Treatment

Tuberculosis (TB) bacteria thrive within humans partly due to their ability to rapidly evolve in certain infection sites, enabling them to evade immune detection and resist treatments. Current TB therapy requires months of antibiotic regimens, yet only achieves an 85% success rate. Aldridge and her team suggest that a deeper understanding of the pathogen's fundamental biology is essential to generate more effective treatment strategies.

Research Process

The research process was labor-intensive and time-consuming. Christin (Eun Seon) Chung, a postdoctoral fellow and one of the paper's first authors, spent three years in a high-containment lab observing individual TB cells.

Innovative Methods for Observation

TB bacteria replicate roughly every 24 hours, far slower than many model bacteria, prompting Aldridge's team to innovate microscopy methods for week-long imaging sessions. Given the bacterium's minuscule size and erratic movement, automated tracking was impractical, requiring Chung to manually analyze the footage and trace the lineage of each cell.

Key Findings

Unique Growth Patterns of TB Bacteria

The experiments revealed that TB bacteria deviate from conventional cell growth patterns. Unlike other bacterial species that exhibit exponential growth—slower in smaller cells and faster in larger ones—TB bacteria maintain consistent growth rates throughout their lifecycle, whether they are newly born and small or nearing division.

"This is the first organism known to exhibit such behavior," states Chung.

Alternative Mechanisms of Growth Control

"TB's growth pattern challenges fundamental assumption in bacterial biology, which traditionally link ribosomes—the protein synthesis machinery—to cell growth rates. Our findings suggest that TB may relay on alternative mechanisms, raising intriguing questions about how its growth is controlled," states Chung.

Novel Growth Characteristic

In addition to identifying significant variability in the growth behaviors of individual bacterial cells, the team uncovered a novel characteristic of TB bacteria: they can initiate growth from either end post-division. This findings was surprising, as related bacteria typically grow exclusively from the end opposite their division site.

The Significance of These Findings

These findings demonstrate that TB microbes employ alternative strategies to enhance variability among their progeny, contradicting assumptions derived from faster-growing, more uniform model organisms. According to Aldridge, the study provides a foundation for her lab and others to further explore and harness these mechanisms to improve treatments.

The Diversity of Microbial Life

"Much of basic microbiology relies on fast-growing model organisms, which are valuable but not necessarily representative of all bacterial types," Aldridge states. "This study underscores the immense diversity of microbial life that remains understudied at a fundamental level, highlighting the importance of investigating pathogens directly."

Conclusion

Prathitha Kar from Harvard University, co-first author of the paper, along with Maliwan Kamkaew, formerly of Tufts University School of Medicine, also played significant roles int he research.

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zinc-antimicrobial-resistance-plasmid transfer

Dietary Zinc as an Inhibitor of Antimicrobial Resistance Gene Transmission

Research Findings from Iowa State University

The Role of Dietary Zinc in Inhibiting AMR Plasmids

Antimicrobial resistance (AMR) genes can spread among microbes via plasmids, circular genetic elements, during lateral gene transfer in the gut, Iova researchers, in their report in Applied and Environmental Microbiology, notes that dietary zinc supplementation may inhibit the transmission of certain AMR plasmids.

Insights from Dr. Melha Mellata

"This is the first instance where we have identified zinc as an inhibitor of plasmid transfer, and at lower concentrations, it excerts minimal impact on bacteria," stated Dr. Melha Mellata, microbiologist and senior author of the study at Iowa State University.

Importance of Preventing Plasmid Transfer

"This is important," she remarked, "because killing gut bacteria could lead to microbiome imbalances, with possible negative health consequences, However, by preventing plasmid transfer, we can minimize the spread of antimicrobial resistance."

The Growing Threat of AMR Infections

Statistics on AMR Infections

Antimicrobial resistance (AMR) infections are an escalating issue, with millions diagnosed annually and 35,000 fatalities each year, according to the CDC.

Impact of AMR Gene Exchange

Dr. Mellata noted that when bacteria exchange AMR genes, they often confer resistance to multiple drugs, meaning a patient may already have a resistant infection before starting antibiotic treatment. Halting plasmid transfer could help curb the spread of AMR genes.

Exploring Gut Health and AMR

Previous Studies on Probiotics and Vaccines

Researchers in Dr. Mellata's lab have been exploring the connection between gut microbiome health and overall well-being. In a recent study, they discovered that administering probiotics alongside a live Salmonella vaccine to chickens resulted in fewer plasmids among Enterobacteriaceae in the gut.

Investigating Oral Treatments for Plasmid Transfer Inhibition

This findings, Dr. Mellata noted, led them to consider testing other oral treatments to inhibit plasmid transfer.

Methodology of the Study

Logan Ott's Leadership Research

Logan Ott, a researcher in Dr. Mellata's lab, spearheaded the study. He and a team of undergraduates gathered commonly available supplements to evaluate their potential to inhibit plasmid transfer.

Experimental Design

The products were dissolved in a test solution, and hundreds of reactions were conducted, involving the conjugation of avian pathogenic Escherichia coli harboring a multi-drug-resistant plasmid with a plasmid-free human E. coli isolate.

Key Observations and Results

Impact of Zinc on Plasmid Transmission

The team observed a significant reduction in plasmid transmission in bacterial strains treated with zinc supplements, compared to those without. Moreover, increased doses of zinc were associated with further decreases in plasmid transmission.

Unexpected Mechanisms Identified

Ott described the observations as both promising and somewhat perplexing. Prior studies had demonstrated that heavy metals can stimulate conjugation, leading to plasmid transfer. The researchers then utilized qPCR to explore zinc's effect on the process at the genetic scale.

Ott remarked, "We uncovered some intriguing mechanisms through which zinc may be facilitating this inhibition, even though prior literature suggested we should anticipate increased activity."

Implications and Future Research

Mechanisms of Zinc Inhibition

The analysis indicated that zinc triggered a significant over-expression of replication genes, likely overwhelming and disrupting the process. Furthermore, although zinc seemed to enhance the genes linked to conjugation, it inhibited certain proteins required for forming the bacterial structures essential for conjugation, thereby hindering the overall transmission.

Next Steps in Research

Mellata outlined the subsequent steps, which involve testing plasmid transfer with additional AMR genes and conducting experiments with animal models to determine whether the lab findings are replicated in vivo. Ott emphasized that scientists have a limited understanding of how bacteria interact and exchange genes within the gut, and future research could shed light on these mechanisms.

Conclusion

The Promise of Zinc in Combating AMR

Mellata feels encouraged by the prospect that zinc, a low-cost and easily accessible supplement, might play a significant role in combating an emerging threat. "Often, the solution can be found in the familiar items we already have," she noted. "All we need to do is make the effort to test them."

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