The bacterium Streptococcus pyogenes can cause a number of life-threatening infections, including septic arthritis, myositis, and necrotizing fasciitis. But its most common manifestation is actually the strain that causes strep throat and tonsillitis, according to Microbe. And it’s believed that up to 15% of the population asymptomatically carries the bacterium.

Although there are treatments for S. pyogenes, typically penicillin, more severe S. pyogenes, known as invasive strep, may require stronger antibiotics in addition to the penicillin as well as to surgery to remove any dead tissue, per Case Reports in Infectious Diseases. Noninvasive infections include strep throat, scarlet fever, and sinusitis and in the 21st century are typically treatable.

According to Academic Forensic Pathology, it’s unclear why S. pyogenes causes life-threatening infections and some but not in others, but up to 1,600 people die every year from S. pyogenes in the United States alone. Worldwide, it’s estimated that every year up to 500,000 people die from S. pyogenes related illnesses. Overall, the highest mortality rates are in the first two days, but most deaths end up occurring within a week of the initial infection often through multiorgan failure.

Although Escherichia coli normally lives inside the intestines, some strains can do some serious damage if they end up there. Those strains include Shiga toxin-producing E. coli, or STEC, due to the Shiga toxin that they produce, which damages the lining of the small intestine and causes diarrhea, according to the Cleveland Clinic.

STEC and other strains of E. coli are primarily contracted through contaminated water or food and since it cannot survive in higher temperatures, cooking food in temperatures of 70 °C or higher can ensure that the E. coli is destroyed. However, although it’s not always fatal and the diarrhea and abdominal cramps can usually resolve within two weeks, in some people, E. coli can cause hemolytic uremic syndrome (HUS), which is life-threatening, according to WHO.

It’s estimated that worldwide, up to 200,000 people die from E. coli related infections every year out of over 300 million who contact E. coli, but infection rates also vary heavily by region. And the journal GMS Infectious Diseases writes that although E. coli related illnesses can be treated with antibiotics, STEC infections can sometimes be made worse by antimicrobial agents. Antibiotic resistance is also an issue in E. coli infections and although the incidence is not too high yet, it’s still a big cause for concern since E. coli is one of the most common bacterium and can easily transfer its resistance to other strains, per the Journal of the São Paulo Institute of Tropical Medicine.

Penicillin started being used as a treatment for the STI gonorrhea in the 1940s, and by 1946 penicillin-resistant gonorrhea. Further resistances were reported in the 1970s and 1980s and despite the current successful uses of azithromycin and ceftriaxone, the next stage of gonorrhea resistance is here, and it’s known as super gonorrhea. According to WHO, super gonorrhea refers to when the bacterium Neisseria gonorrhoeae becomes a “superbug,” causing “extensively drug-resistant gonorrhea with high-level resistance.” And this resistance applies to penicillin, azithromycin, ceftriaxone, and several other antibiotics. As of 2018, super gonorrhea had been reported in numerous countries including Australia, France, and the United Kingdom.

Although untreated gonorrhea rarely causes death, it can lead to a number of long-term conditions and discomfort. For people with uteruses, untreated gonorrhea can lead to pelvic inflammatory disease, which can cause long-term pain and infertility. And for people with testicles, it can lead to epididymitis, which causes scrotal pain and swelling. Stanford Health Care also writes that in rare cases, the bacterium can enter the bloodstream and infect other parts of the body, causing joint pain and skin sores, among other symptoms. It’s at this point that gonorrhea can turn deadly.

The first instance of incurable gonorrhea was reported in 2018 and it’s only a matter of time before even the best antibiotics simply aren’t enough.

You may not instantly recognize the name Bacillus anthracis but that’s because the bacterium is often overshadowed by the disease it causes: anthrax. When B. anthracis dries, it forms spores that can stay viable in animal hair or soil for years until it enters the body. Once it’s inside, the spores start multiplying, causing the condition known as anthrax. According to the CDC, depending on where the anthrax enters the body, symptoms will vary, but all types of anthrax have the potential to be fatal.

But MSD Manual writes that the mortality for inhalation and meningeal anthrax is the highest, with practically 100% of cases being fatal if left untreated. But with treatment, mortality rates drop to about 50%. In comparison, cutaneous anthrax, which is the most common form of anthrax, is fatal in less than 1% of cases when treated and only 5% to 20% of untreated cases.

Historically, people have tried to use B. anthracis as a bioweapon several times. During World War II, Unit 731 of the Imperial Japanese Army experimented with both anthrax and botulism as part of their biological weapons program. And in 2001, Bruce Edwards Ivins was reportedly responsible for mailing letters filled with anthrax spores to several news media outlets and Democratic Senators. Five people died as a result and 17 others fell ill in what the FBI calls “the worst biological attack in U.S. history.”

Several bacteria cause pneumonia, but one of the most serious causes continues to be the bacterium Pseudomonas aeruginosa. And pneumonia isn’t the only illness that P. aeruginosa can cause. It’s also responsible for urinary tract infections and in some cases can pass into the blood, especially after surgery, according to the CDC. And according to Current Microbiology, not only does P. aeruginosa intrinsically have high antibiotic resistance, but it has the ability to develop new resistances during treatment. As a result, “these infections are difficult to eradicate.”

When P. aeruginosa first emerged in the 1960s, it had a mortality rate of roughly 90%. But as antipseudomonal antibiotics were developed, the mortality rate was brought down and is now between 18% to 61%, writes Clinical Infectious Diseases.

With multidrug-resistant Pseudomonas aeruginosa (MDRPA) there are limited treatment options but treating even a basic Pseudomonas infection is difficult because it’s “clinically indistinguishable from other forms of gram-negative bacterial infection.” As a result, people are often initially given antibiotics that are ineffective against P. aeruginosa, resulting in a delay in proper treatment coupled with “inappropriate antimicrobial therapy[, which] is associated with adverse outcome[s].”

Caused by a subset of the bacterium Vibrio cholerae, cholera continues to cause over 100,000 deaths worldwide annually. But according to WHO, there’s a global goal to reduce cholera deaths by 90% by 2030.

In the 1990s, the subsets of V. cholerae that cause cholera were divided by scientists into O group 1 and non-O1, depending on whether they “agglutinated with serum from cholera patients.” V. cholerae thrives in water and once infected, people can spread V. cholera through their feces, especially if it gets into the water system. V. cholera can also be transmitted through raw or undercooked shellfish, but such cases are relatively rare.

The Cleveland Clinic writes that cholera symptoms are generally mild, but 10% of people develop, in addition to diarrhea, muscle cramps, vomiting, and weakness. And in the end, the diarrhea and vomiting from cholera can lead to such severe dehydration that it causes kidney failure, coma, and death. Because dehydration is the immediate cause of death, cholera is often treated by replenishing fluids and salts rather than antibiotics. While antibiotics can shorten the length of the illness and help with severity, rehydration is the most important thing. And the CDC reports that if it’s promptly and properly treated, less than 1% of cholera cases are fatal.