Unveiling the Hidden Battle: The Race to Stop Bacteria From Outsmarting Our Immune System

Joining a Fantastic Team

30 years ago, I embarked on an exciting journey by joining the University of Sheffield. This pivotal moment came after Professor Tim Higenbottam DSc MD MA FRCP FFPM , my Ph.D. supervisor, was appointed as Professor of Medicine and Director of the Clinical Science Department. I was welcomed into a brilliant team in the Respiratory Physiology Department, including Dr. Denise Bee, Dr. Celia Emery, and Dr. Gwenda Barer, all renowned experts in experimental models of pulmonary hypertension.

A Multidisciplinary Approach

Being part of the Clinical Science team led to unique multidisciplinary projects. We collaborated across various university faculties, bringing together diverse expertise. Notable contributors included Dr. Alan Spivey from the Chemistry Department, Dr. Robert Read from Infectious Diseases, and Dr. Robert Poole from the Krebs Institute for Biomolecular Research.

Advancing the Understanding of Nitric Oxide Detoxification

With Robert Poole and Tania Stevanin, we made significant strides in understanding bacterial nitric oxide (NO) detoxification—a critical process enabling pathogens to evade the host immune response. Our research shed light on how bacteria neutralize NO, a potent antimicrobial molecule produced by host immune cells, thereby enhancing their survival and pathogenicity.

Challenges and Triumphs ??

The path to these discoveries was not without its challenges. One of the major hurdles was developing sensitive assays to measure nitric oxide levels accurately. We also had to navigate the complexities of working with scientists from different backgrounds and nationalities. Despite these challenges, the collaboration was immensely rewarding, leading to groundbreaking findings.

Key Discoveries ??

One of our major findings was that the flavohemoglobin Hmp in Salmonella enterica serovar Typhimurium protects the bacterium from NO-related killing by human macrophages. This discovery underscored the role of Hmp in bacterial defense mechanisms against host-induced nitric oxide stress.

Furthering this line of inquiry, Dr. Stevanin, Dr. Read, and Dr. Moir demonstrated that nitric oxide reductase (NorB) in Neisseria meningitidis enhances bacterial survival within human macrophages and the nasopharyngeal mucosa. This work highlighted the importance of NO detoxification systems in bacterial pathogenesis and persistence within the host.

Impact and Recognition ??

These studies have since been referenced in numerous research projects exploring bacterial NO detoxification mechanisms. Our work has been instrumental in elucidating the strategies employed by bacteria to counteract host defenses, providing valuable insights that could inform the development of novel antimicrobial therapies targeting NO detoxification pathways.

Personal and Professional Growth ??

This journey significantly impacted my career. The collaborative environment and the cutting-edge research at Sheffield shaped my scientific perspective and honed my skills. The publication of our work in 2002 was a major triumph, cementing our contributions to the field and opening new avenues for research.

Inspiring the Next Generation ??

For younger researchers, our story illustrates the power of collaboration, perseverance, and interdisciplinary approaches in scientific discovery. It emphasizes the importance of tackling challenges head-on and celebrating every triumph along the way.