How your infection fights back: Bacterial defense against hypochlorous acid (HOCl)

Featured Scientist: Sadia Sultana (she/her/hers), PhD student (Anticipated: Spring 2024), School of Biological Sciences, Illinois State University

A picture of Sadi looking directly into the camera.

Birthplace: Dhaka, Bangladesh

My Research: Humans, animals, and several insects have an innate immune system. The innate immune system is the body’s first line defense against pathogens. Pathogens are a type of microorganism that can cause disease. After our body recognizes the pathogen, it activates the immune system to destroy it. In my research, I work to understand how pathogenic bacteria defend themselves against the innate immune system in humans.     

Research Goals: I am interested in studying how pathogenic bacteria interact with their hosts.

Career Goals: My long-term career goal is to establish myself as an academic researcher. My research focus would be how pathogenic bacteria interact with their human hosts.        

Hobbies: I like traveling and sports!

Favorite Thing About Science: Science brings people from different backgrounds together. It is interesting to learn how scientists from diverse research fields work together to answer new questions.

My Team: We have a diverse research group that consists of graduate and undergraduate students. We also host visiting research fellows.

Organism of Study: In my research, I work on a type of bacteria called uropathogenic Escherichia coli (UPEC). UPEC can cause urinary tract infections (UTIs) in humans.

Circles of bacteria on a plate (6 rows and 6 columns). The circles of bacteria on the far right are thin, with only a few bacteria. The circles on the far left are are full and opaque.
A spot plate of UPEC bacteria

Field of Study: Microbiology

What is Microbiology? Microbiology is the study of the forms of life that you cannot see without the use of a microscope. Microbiologists study how microscopic organisms play helpful or harmful roles in our lives.

Check Out My Original Paper: “Bacterial Defense Systems against the Neutrophilic Oxidant Hypochlorous Acid”

QR code that links to the original publication

Citation: Sultana, Sadia, Alessandro Foti, and Jan-Ulrik Dahl. “Bacterial defense systems against the neutrophilic oxidant hypochlorous acid.” Infection and Immunity 88.7 (2020).    

Research At A Glance: Our paper is a review article, a type of scientific paper that focuses on a very specific topic. Review articles summarize the results of prior research and propose possible directions for future research. In our article, we covered how pathogenic bacteria defend themselves from the human immune system. When people become infected by a pathogen, the immune system is rapidly activated to fight off the infection. The innate immune system is the first line of defense against infections. As part of the innate immune response, a type of protective cell, the neutrophil (also called a phagocytic cell) is activated. Neutrophil will surround and engulf the pathogen to destroy it.  Once the bacterium has been engulfed, the neutrophil will produce strong chemicals, like hypochlorous acid (HOCl), to destroy it. However, bacteria have also evolved ways to defend themselves from HOCl. In our paper, we focus on some of the defense strategies that bacteria use against HOCl and describe how bacteria use those strategies to survive in the human immune system.                                                       

Highlights: Our paper contains several illustrations that show how bacteria generally protect themselves from HOCl exposure, but our most important image was Figure 1. Figure 1 is broken into three steps. It shows how an innate immune cell, the neutrophil, will engulf a pathogen and how it will make HOCl to destroy it.

Figure 1. Upper panel: the three-step process that neutrophils use to 1) sense and attach to the bacteria, 2) ingest the bacteria, and 3) kill the bacteria. Lower panel: how the neutrophil kills the bacteria. The neutrophil will release the antimicrobial enzymes, NOX2 and MPO, into the membrane that surrounds the bacteria. These antimicrobial enzymes help to make HOClFigure adapted from Sultana et al. 2021.  

When the human body becomes infected with pathogenic bacteria, neutrophils will migrate to the site of infection. The neutrophil will bind to the bacteria or “microbe” (step 1). It will then ingest the bacteria and enclose it within a small membrane (step 2). This process is called phagocytosis. In the final step, small particles called granules will release antimicrobial enzymes into the membrane that surrounds the bacterium (step 3). Enzymes are a type of protein that speed up chemical reactions. Antimicrobial enzymes cause a chemical reaction that damages the cellular structure of the bacteria. The top panel of Figure 1 shows steps 1-3 of this process. The bottom panel shows the chemical reactions that take place inside the membrane that surrounds the bacteria. Two important antimicrobial enzymes are NOX2 and MPO. They bring about a series of chemical reactions that create HOCl from oxygen (Figure 2).

A series of chemical reactions. Oxygen is converted to Super Oxide by NOX2. Super Oxide is converted to Hydrogen Peroxide by Superoxide dismutase. Finally, Hydrogen Peroxide is converted to Hypochlorous Acid by MPO.
Figure 2. A series of chemical reactions that can make HOCl from oxygen. One of the chemicals in this process is Hydrogen Peroxide (H2O2). Many people are familiar with H2O2 because it is often used as an over-the-counter disinfectant for small cuts and scrapes. HOCl is also a very strong disinfectant and better at killing bacteria than H2O2. HOCl is the common ingredient of the household disinfectant, bleach.

What My Science Looks Like:  My PhD research aims to understand how pathogenic bacteria defend themselves against HOCl exposure. I study a specific type of bacteria, UPEC. In our lab, I recently discovered a group of genes in UPEC that appear to help the bacteria to defend against HOCl exposure. Now, my goal is to find out how these genes function.

The Big Picture: UTIs are the most common types of bacterial infection worldwide. They are particularly common among young and otherwise healthy women. In fact, about 60% of all women are diagnosed with a UTI at least once in their lifetime. Upon entering the urinary tract, UPEC rises from the urethra into the bladder. In response, our innate immune cells, neutrophils, infiltrate into the bladder and generate HOCl. Surprisingly, how UPEC defend themselves from HOCl exposure is completely unexplored. It’s important to learn how these bacteria defend against HOCl exposure. Doing so could reveal new drug targets that make UPEC vulnerable to this immune response. This treatment might increase the body’s ability to clear bacterial infections and lower the chance that the bacteria will become resistant to treatment.

Decoding the Language: 

Antimicrobial enzymes: Antimicrobial enzymes are any type of protein that can kill bacteria. They function by targeting different cellular components of the bacteria.

Gene: A gene is a unit of heredity passed from parents to offspring. Genes normally code for proteins that have certain functions in the body.

Granule: A granule is a small particle that contains different enzymes. It is barely visible under a microscope.

Hydrogen peroxide (H2O2): H2O2 is a type of reactive oxygen species, a molecule made from oxygen that can damage bacteria. Many people use H2O2 as an over-the-counter disinfectant.

Hypochlorous acid (HOCl): HOCl is a reactive chlorine species that can damage bacteria but is more effective at killing bacteria than H2O2. HOCl also commonly known as bleach.

Innate immune system: The innate immune system is the first line of defense against an infection. It is a fast and generalized response that involves many types of immune cells, such as      neutrophils. When you get a small cut on your finger and it swells, that is an example of an innate immune response.  It is different than the adaptive immune system, which is much slower.  In the adaptive immune response, the body will recognize a pathogen and create a defense that is specific to that pathogen. For example, if someone has previously had measles and has recovered, then that person will be protected for the rest of their lives from that illness. This is because the body has designed a specific defense to the pathogen that causes measles.  

Myeloperoxidase (MPO): MPO is an enzyme that is expressed by a neutrophil immune cell. It produces HOCl.

Neutrophil: A neutrophil is a type of white blood cell that is involved in the immune response to infection or injury. Neutrophils are very abundant and can make up 40% – 70% of all white blood cells. Neutrophils will move to the site of injury or infection very quickly and ingest pathogens to destroy them.

NADPH oxidase (NOX2): NOX2 is an enzyme that is expressed by a neutrophil immune cell. It converts oxygen (O2) to super oxide (O2). Super oxide is one of the chemicals in the series of chemical reactions that is needed to make HOCl.

Pathogenic: Pathogenic refers to a pathogen. A pathogen is any type of microorganism, like a bacterium, or virus, or more generally, a “germ”, that causes disease or infection.

Phagocytic cell: Phagocytic cell refers to a class of immune cells that are capable of ingesting invading pathogens to clear them from the body.

Phagocytosis: Phagocytosis is the process that specialized immune cells use to clear infectious microorganisms from the body. The process involves recognizing the invader, surrounding and engulfing the invader, then destroying the invader once it is inside the cell.

Spot plate: A “spot plate” is the plate used in a spot plate assay. A spot plate assay is a research method used to see how sensitive bacteria is to a type of antimicrobial (chemicals that kill microorganisms). The scientist will apply antimicrobials at different concentrations, then count how many bacteria able to survive at each concentration.

Urethra: The urethra is the duct that connects to the bladder and allows people to urinate. 

Urinary tract infection (UTI): UTIs are common infections that take place in the urinary system. Most infections take place within the lower urinary tract, in the urethra and the bladder, but the infection can also reach the kidneys. Symptoms generally include painful urination, but symptoms become more serious if the infection reaches the kidneys. UTIs can occur naturally and can also occur in a medical setting when patients have a catheter placed to allow for assisted urination.

Uropathogenic Escherichia coli (UPEC): UPEC is the most common bacteria that causes UTIs. It causes about 80% – 90% of the UTIs that occur naturally.

Learn More:

Article on innate and adaptive immunity

Research paper on pathogenic Escherichia coli: Kaper JB, Nataro JP, Mobley HL. 2004. Pathogenic escherichia coli. Nature reviews microbiology. 2(2):123-40.

Research paper on hypochlorous acid on hosts and pathogens: Ulfig A, Leichert LI. 2020.The effects of neutrophil-generated hypochlorous acid and other hypohalous acids on host and pathogens. Cellular and Molecular Life Sciences. 13:1-30.

Synopsis edited by Rosario Marroquin-Flores, PhD (Anticipated: Spring 2022), Illinois State University, and Jaclyn Everly, PhD (Anticipated: Spring 2024), Illinois State University.

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