text: Cigarette smoke has long been known to have a multitude of damaging effects, but thanks to recent research we now know it also fuels the virulent rampage of superbugs. According to a study published in the journal Infection and Immunity by researchers at the University of California, San Diego School of Medicine, antibiotic-resistant bacteria, specifically MRSA, are vastly more difficult to kill when exposed to cigarette smoke. 
   
   Methicillin-resistant Staphylococcus aureus, or MRSA, is a type of bacteria that causes life-threatening infections to the skin, bloodstream, or a surgical site, and sometimes causes pneumonia. Originating as a strain of staph infection, MRSA becomes resistant to antibiotics and often affects individuals in hospitals or other health care settings. A disastrous diagnosis due to its innate difficulty to treat, it has become even more threatening with the addition of smoking. 
   
   "We already know that smoking cigarettes harms human respiratory and immune cells, and now we've shown that, on the flipside, smoke can also stress out invasive bacteria and make them more aggressive," said Dr. Laura E. Crotty Alexander of UC San Diego and the Veterans Affairs San Diego Healthcare System, in a press release. Crotty Alexander, a pulmonologist, sought to find potential ties between the increased occurrences of MRSA cases in smokers. In order to do so, Crotty Alexander and her team tested two groups of MRSA, one exposed to cigarette smoke extract and one not, to see how each group responded to the defenses of our immune system. 
   
   Macrophages, or immune cells known to devour infectious ages, were infected with both types of MRSA (smoke exposed and not) to test the immune response. Although both were able to take up the populations of MRSA, macrophages fighting MRSA exposed to cigarette smoke extract had a significantly harder time killing them. 
   
   Researchers found that this type of MRSA was more resistant to the reactive oxygen species, a chemical burst macrophages utilize once they have engulfed bacteria. MRSA exposed to smoke extract was also more resistant to antimicrobial peptides, another line of immune defense used to make holes in bacteria and cause inflammation. Even more alarming was researchers’ discovery that MRSA was able to adhere better to human cells when treated with smoke, assisting in the success of their invasion. This effect depended strongly on dose; the more smoke extract the MRSA was exposed to, the more resistant it became. 
   
   Ultimately, the data suggest that through altering the cell walls of the bacteria, cigarette smoke allows MRSA to repel common forms of immune responses. Another study conducted by researchers at University of California, San Diego School of Medicine a year earlier suggested something similar with e-cigarette smoke; vaporized smoke can also alter the structure of MRSA’s cell wall to make it more resistant to bacteria. However, this research also discovered that surface changes to the bacteria increased 10 times more with exposure to cigarette smoke rather than e-cigarette vapor. 
   
   "Cigarette smokers are known to be more susceptible to infectious diseases. Now we have evidence that cigarette smoke-induced resistance in MRSA may be an additional contributing factor," Crotty Alexander said. Through their finding, Crotty Alexander and her team hope to add yet another reason to why individuals should refrain from smoking. 
   
   Source: Crotty Alexander L, Matthew D, Hwang J, et al. Analysis of the Effects of Cigarette Smoke on Staphylococcal Virulence Phenotypes. Infection and Immunity. 2015. ||||| Cigarette smoke functions much like an alarm to the superbug MRSA, warning it to activate its defenses, according to a new study led by UC San Diego scientists. 
   
   In lab studies in human cells and whole mice, MRSA (Methicillin-resistant Staphylococcus aureus) bacteria exposed to cigarette smoke extract become harder to kill, said Dr. Laura E. Crotty Alexander, a pulmonologist at UCSD and the Veterans Affairs San Diego Healthcare System. 
   
   Crotty Alexander is senior author of the paper, published Monday in the journal Infection and Immunity. 
   
   The study is similar to one published last May, in which the effects of e-cigarette vapor on bacterial resistance was examined. 
   
   Laura Crotty Alexander led a study that found the superbug MRSA becomes more resistant when exposed to electronic cigarette vapors. Crotty Alexander is a UCSD assistant clinical professor of medicine and staff physician at VA San Diego Healthcare System. — Hayne Palmour IV Share Photo  
   
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   ✉ Laura Crotty Alexander led a study that found the superbug MRSA becomes more resistant when exposed to electronic cigarette vapors. Crotty Alexander is a UCSD assistant clinical professor of medicine and staff physician at VA San Diego Healthcare System. — Hayne Palmour IV 
   
   Cigarette smoke exposure stresses MRSA, causing it to alter its cell walls to repel toxic substances, Crotty Alexander said. This enhances survival against reactive oxygen species, which macrophages generate to kill pathogens. 
   
   MRSA exposed to the smoke extract were four times more resistant to macrophage killing than non-exposed MRSA, the study stated. 
   
   In addition, Crotty's team found that cigarette smoke extract-exposed MRSA became more resistant antimicrobial peptides, which pierce bacterial cell walls. 
   
   Worse, the study found that the increased resistance continued for 24 hours after exposure, suggesting it could be inherited. MRSA divides about every 30 minutes under ideal conditions. At that rate, a single MRSA cell could generate nearly 17 million descendents in 12 hours. 
   
   "When we put these cigarette smoke-exposed bacteria into mice, there was a significant difference in mortality," compared to MRSA that had not been smoke exposed, Crotty Alexander said in a phone interview Thursday. 
   
   The smoke-exposed MRSA also became better at invading human cells in lab cultures. 
   
   "The cigarette smoke helped the bacteria kill more mice, whereas the e-cigarette vapor was just on the borderline," Crotty Alexander said. "It did make it a little more aggressive, but not as much as the cigarette smoke." 
   
   Scanning electron micrograph of methicillin-resistant Staphylococcus aureus and a dead human neutrophil. — NIAID Share Photo  
   
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   ✉ Scanning electron micrograph of methicillin-resistant Staphylococcus aureus and a dead human neutrophil. / NIAID 
   
   The study stated it was performed to examine an alternative to the prevailing theory that cigarette smoke mostly causes disease by harming the smoker. The alternative is that smoke actually makes the pathogen tougher. The study focused on MRSA and its more sensitive relative MSSA as a good test case for that alternative. 
   
   "Because MRSA causes severe pneumonia more often than MSSA, and because MRSA commonly colonizes the nasopharynx and airways and thus is exposed to inhaled substances, we examined the effect of cigarette smoke on MRSA resistance to host innate immune killing mechanisms and the ability to cause pneumonia in mice," the study stated. 
   
   Tests on human cells found the same result, Crotty Alexander said. Previous research has shown that cigarette smoke harms human respiratory and immune cells, she said. 
   
   So the picture now is that cigarette smoke both harms smokers and assists pathogens. 
   
   Study co-authors include Elisa K. McEachern, John H. Hwang, Katherine M. Sladewski, UC San Diego and Veterans Affairs San Diego Healthcare System; Shari Nicatia, UC San Diego, Veterans Affairs San Diego Healthcare System and Utrecht University; Carola Dewitz, UC San Diego, Veterans Affairs San Diego Healthcare System and University of Veterinary Medicine, Hannover, Germany; Denzil P. Mathew, Veterans Affairs San Diego Healthcare System; and Victor Nizet, UC San Diego. 
   
   The study was funded in part by the U.S. Department of Veterans Affairs.
target: – Superbugs such as MRSA are already bad enough. But it turns out that something can make them even nastier: cigarette smoke. Researchers found that antibiotic-resistant bacteria exposed to the smoke became more aggressive and far more difficult to kill, they explain at Eureka Alert. It's almost as if the smoke sets off an alarm that causes the bacteria to strengthen its defenses, explains the Union-Tribune of San Diego. Scientists made the discovery by exposing immune cells to two different batches of MRSA, one normal and one treated with cigarette smoke extract. The bigger the dose of smoke, the bigger the effect, notes Medical Daily. "We already know that smoking cigarettes harms human respiratory and immune cells, and now we've shown that, on the flipside, smoke can also stress out invasive bacteria and make them more aggressive," says lead author Laura Crotty Alexander of UC San Diego. It's a double-whammy: Smokers already have weakened immune systems that make them more susceptible to infectious diseases, and the smoke they inhale seems to make invading pathogens even more dangerous. In this study, the smoke helped MRSA survive longer and kill more mice with pneumonia. (The latest antibiotic-resistant bug to make headlines is a nasty stomach virus.)