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小鼠研究中糖尿病与抗生素耐药性的关系

Diabetes Linked to Antimicrobial Resistance in Mouse Study

GEN 等信源发布 2025-02-13 11:59

可切换为仅中文


Staphylococcus aureus

金黄色葡萄球菌

is a leading cause of antibiotic resistance-associated infections and deaths. It is also the most prevalent bacterial infection among individuals with diabetes mellitus (DM), a chronic condition that affects blood sugar control and reduces the body’s ability to fight infections.

是抗生素耐药性相关感染和死亡的主要原因。它也是糖尿病患者中最常见的细菌感染,糖尿病是一种影响血糖控制并降低身体抵抗感染能力的慢性病。

A study by scientists at the University of North Carolina School of Medicine found that in diabetic mice with an

北卡罗莱纳大学医学院科学家的一项研究发现,在患有糖尿病的小鼠中

S. aureus

金黄色葡萄球菌

skin and soft tissue infection (SSTI), the bacterium evolves antibiotic resistance rapidly, whereas resistance didn’t occur in nondiabetic mice over the course of infection. Results from the study, headed by microbiologists Brian Conlon, PhD, and Lance Thurlow, PhD, showed how the diabetic microbial environment produces resistant mutations.

皮肤和软组织感染(SSTI),这种细菌迅速产生抗生素耐药性,而在感染过程中,非糖尿病小鼠没有发生耐药性。这项由微生物学家布莱恩·康隆博士和兰斯·瑟洛博士领导的研究结果表明,糖尿病微生物环境如何产生耐药突变。

The findings also demonstrated that controlling the blood sugar of diabetic mice with insulin resulted in significantly decreased incidence of antibiotic-resistant .

研究结果还表明,用胰岛素控制糖尿病小鼠的血糖可显着降低抗生素耐药性的发生率。

S. aureus

金黄色葡萄球菌

. The study results point to potential approaches to combatting antibiotic resistance in individuals with diabetes.

研究结果指出了对抗糖尿病患者抗生素耐药性的潜在方法。

“We found that antibiotic resistance emerges much more rapidly in diabetic models than in nondiabetic models of disease,” said Conlon, associate professor at the department of microbiology and immunology. “This interplay between bacteria and diabetes could be a major driver of the rapid evolution and spread of antibiotic resistance that we are seeing.”.

微生物学和免疫学系副教授康伦(Conlon)说:“我们发现,糖尿病模型中的抗生素耐药性比非糖尿病疾病模型中的耐药性出现得更快。”。“细菌和糖尿病之间的这种相互作用可能是我们正在看到的抗生素耐药性快速演变和传播的主要驱动因素。”。

Conlon, Thurlow, and colleagues reported on their study in

Conlon、Thurlow及其同事报告了他们在

Science Advances

科学进步

. In their paper, titled “

在他们的论文中,标题为“

Diabetes potentiates the emergence and expansion of antibiotic resistance

糖尿病加剧了抗生素耐药性的出现和扩大

,” the team noted, “In total, this work establishes a direct relationship between diabetes and the emergence and proliferation of AMR … The data presented here may inform the development of treatment strategies and highlight the crucial need for the development and implementation of more effective antibacterial compounds to improve infection outcomes in individuals with diabetes.”.

该团队指出,“总的来说,这项工作建立了糖尿病与AMR的出现和扩散之间的直接关系……这里提供的数据可能会为治疗策略的制定提供信息,并强调开发和实施更有效抗菌化合物的关键需要,以改善糖尿病患者的感染结果。”。

Brian Conlon, PhD [UNC Department of Microbiology and Immunology.]

Brian Conlon博士[联合国大学微生物学和免疫学系]

Antibiotics are powerful, fast-acting medications designed to eradicate bacterial infections. However, in recent years, their dependability has waned as bacterial resistance spreads. People with DM are more susceptible to bacterial infection, leading to a high frequency of severe and chronic infections in individuals with DM, the authors noted.

。然而,近年来,随着细菌耐药性的传播,它们的可靠性已经下降。作者指出,糖尿病患者更容易受到细菌感染,导致糖尿病患者发生严重和慢性感染的频率很高。

“Individuals with diabetes mellitus frequently develop severe skin and soft tissue infections (SSTIs) that are recalcitrant to antibiotic treatment … Antimicrobial resistance (AMR) further complicates the treatment of infection in individuals with DM.”.

“糖尿病患者经常会出现严重的皮肤和软组织感染(SSTI),这些感染对抗生素治疗难以抵抗……抗菌素耐药性(AMR)使糖尿病患者的感染治疗更加复杂。”。

Diabetes affects the body’s ability to control glucose, often causing excess glucose to build up in the bloodstream. Staph feeds off these high sugar levels, allowing it to reproduce more rapidly. “

糖尿病影响身体控制葡萄糖的能力,通常会导致血液中产生过量的葡萄糖。葡萄球菌以这些高糖含量为食,使其繁殖更快。“”

S. aureus

金黄色葡萄球菌

uses glucose as a preferential carbon source and becomes hypervirulent in a diabetic SSTI infection,” the scientists further stated. The bacterium can also grow without consequence, as diabetes also impairs the immune system’s ability to destroy cells and control infection. “The increased susceptibility to infection in individuals with diabetes is due to a combination of factors including immunosuppression, hyperglycemia, and lack of vascularization in the extremities,” the scientists further explained.

科学家进一步表示:“使用葡萄糖作为优先碳源,在糖尿病SSTI感染中变得毒性过高。”。这种细菌也可以毫无后果地生长,因为糖尿病还会损害免疫系统破坏细胞和控制感染的能力。科学家进一步解释说:“糖尿病患者对感染的易感性增加是由于多种因素的综合作用,包括免疫抑制、高血糖和四肢血管缺乏。”。

SSTIs in diabetic individuals are frequently severe and may necessitate amputation, especially in the extremities such as toes and feet..

糖尿病患者的SSTI通常很严重,可能需要截肢,尤其是在脚趾和脚等四肢。。

As the numbers of bacteria increase in a diabetic infection, so does the likelihood of resistance. Random mutations appear and some build up resistance to external stressors, like antibiotics. Once a resistant mutant is present in a diabetic infection, it rapidly takes over the population, using the excess glucose to drive its rapid growth..

随着糖尿病感染中细菌数量的增加,产生耐药性的可能性也随之增加。随机突变出现,一些突变会对外部压力产生抵抗力,如抗生素。一旦糖尿病感染中出现耐药突变体,它就会迅速接管人群,利用过量的葡萄糖推动其快速生长。。

Staphylococcus aureus

金黄色葡萄球菌

is uniquely suited to take advantage of this diabetic environment,” said Thurlow, assistant professor of microbiology and immunology, with joint appointments in the UNC School of Medicine and the Adams School of Dentistry. “Once that resistant mutation happens, you have excess glucose and you don’t have the immune system to clear the mutant and it takes over the entire bacterial population in a matter of days.”.

微生物和免疫学助理教授瑟洛(Thurlow)说,他是UNC医学院和亚当斯牙科学院的联合教授。“一旦发生耐药突变,你就会有过量的葡萄糖,你的免疫系统无法清除突变,它会在几天内接管整个细菌种群。”。

Lance Thurlow, PhD [UNC Department of Microbiology and Immunology.]

Lance Thurlow博士[联合国大学微生物学和免疫学系]

Conlon, an expert on antibiotic treatment failure, and Thurlow, an expert on Staph pathogenesis in diabetes, have long been interested in comparing the effectiveness of antibiotics in a model with and without diabetes. Using their connections within the department of microbiology and immunology, the researchers brought their labs together to perform a study with antibiotics in a diabetic mouse model of .

抗生素治疗失败专家Conlon和糖尿病葡萄球菌发病机制专家Thurlow长期以来一直对比较抗生素在糖尿病和非糖尿病模型中的有效性感兴趣。。

S. aureus

金黄色葡萄球菌

infection

感染

.

.

First, the team prepared a mouse model with bacterial SSTIs. The mice were divided into two groups: one group was given a compound, streptozotocin (STZ), that selectively kills cells in the pancreas, rendering the animals diabetic, and the other group was not given the compound. Researchers then infected both diabetic and non-diabetic mice with .

首先,该团队准备了一个带有细菌性SSTI的小鼠模型。将小鼠分为两组:一组给予化合物链脲佐菌素(STZ),该化合物选择性杀死胰腺细胞,使动物患糖尿病,另一组未给予该化合物。然后,研究人员用糖尿病和非糖尿病小鼠感染。

S. aureus

金黄色葡萄球菌

and treated the animals with rifampicin, an antibiotic to which resistance evolves at a high rate.

并用利福平治疗动物,利福平是一种耐药率很高的抗生素。

After five days of infection, the authors noticed that the rifampicin treatment had practically no effect in diabetic models. Testing samples the team found that the bacteria had evolved to become resistant to rifampicin, with the infection harboring over a hundred million rifampicin-resistant (Rif

感染五天后,作者注意到利福平治疗对糖尿病模型几乎没有影响。通过对样本的测试,研究小组发现,这种细菌已经进化为对利福平具有耐药性,感染者中有超过一亿人对利福平具有耐药性(Rif

R

R

) bacteria. The mutation had taken over the entire infection in just four days. In contrast, there were no rifampicin-resistant bacteria in the nondiabetic models. “… we did not detect the emergence of any Rif

)细菌。突变仅在四天内就控制了整个感染。相反,在非糖尿病模型中没有利福平耐药细菌。“…我们没有发现任何Rif的出现

R

R

S. aureus

金黄色葡萄球菌

in non-diabetic mice,” the team further noted.

They next inoculated diabetic and non-diabetic models with

接下来,他们用糖尿病和非糖尿病模型接种

S. aureus

金黄色葡萄球菌

as before, but this time supplemented with a known number of rifampicin-resistant bacteria. While these bacteria rapidly took over the diabetic infection, they remained as only a sub-population in non-diabetic models after four days of rifampicin treatment. “… our data suggest that only in a diabetic environment under antibiotic pressure can this Rif.

和以前一样,但这次补充了已知数量的利福平耐药细菌。虽然这些细菌迅速接管了糖尿病感染,但在利福平治疗四天后,它们仍然只是非糖尿病模型中的一个亚群。“……我们的数据表明,只有在抗生素压力下的糖尿病环境中,这种Rif才能发生。

R

R

mutant thrive and expand,” the investigators stated.

研究人员说:“突变体茁壮成长并扩展。”。

While the findings have left the team with questions, they maintain that the evolution of antibiotic resistance in people with diabetes could spell trouble for the population at large. Antibiotic-resistant strains of bacteria spread from person to person in the same ways as other bacteria and viruses do—in the air, on doorknobs, and the food that we eat—which makes preventing these types of infections a major priority.

虽然这些发现给研究小组留下了疑问,但他们坚持认为,糖尿病患者抗生素耐药性的演变可能会给整个人群带来麻烦。抗生素耐药菌株在人与人之间传播的方式与空气中、门把手上以及我们吃的食物中其他细菌和病毒传播的方式相同,这使得预防这些类型的感染成为当务之急。

“The rapid growth of the diabetic population combined with the concurrent rise of AMR is a serious global health concern,” they noted..

他们指出:“糖尿病人口的快速增长加上AMR的同时上升是一个严重的全球健康问题。”。。

So, what can be done to prevent it? The researchers also showed that reducing blood sugar levels in diabetic models, through the administration of insulin, deprived bacteria of their fuel, keeping their numbers at bay, and reducing the chances of antibiotic-resistant mutations from occurring. “Administering insulin to diabetic mice greatly reduced the emergence of Rif.

那么,可以采取什么措施来预防呢?研究人员还表明,通过服用胰岛素降低糖尿病模型中的血糖水平,可以剥夺细菌的燃料,控制细菌数量,并减少发生抗生素耐药突变的机会。“给糖尿病小鼠服用胰岛素可以大大减少Rif的出现。

R

R

S. aureus

金黄色葡萄球菌

… despite only partially restoring normal blood glucose levels,” the investigators stated. Their findings suggest that controlling blood sugar through insulin use could be key in preventing antibiotic resistance. “These data indicate that controlling diabetes with insulin helps to prevent the emergence of antibiotic-resistant .

…尽管血糖水平仅部分恢复正常,”研究人员表示。他们的研究结果表明,通过使用胰岛素来控制血糖可能是预防抗生素耐药性的关键。“这些数据表明,用胰岛素控制糖尿病有助于防止抗生素耐药性的出现。

S. aureus

金黄色葡萄球菌

.”

.”

Conlon added, “Resistance and its spread are not only associated with the prescription of drugs, but also the health status of those that are taking antibiotics. Controlling blood glucose then becomes really important. When we gave our mice insulin, we were able to bring their blood sugar back to normal and we didn’t get this rapid proliferation of resistant bacteria.”.

Conlon补充道:“耐药性及其传播不仅与药物处方有关,而且与服用抗生素的人的健康状况有关。控制血糖变得非常重要。当我们给小鼠注射胰岛素时,我们能够使他们的血糖恢复正常,而我们没有得到这种耐药性细菌的快速增殖。”。

The investigators are expanding their efforts to study the evolution of resistance in humans (with and without diabetes) and other antibiotic-resistant bacteria of interest, including

研究人员正在扩大努力,研究人类(有或没有糖尿病)和其他感兴趣的抗生素耐药细菌的耐药性演变,包括

Enterococcus faecalis

粪肠球菌

,

,

Pseudomonas aeruginosa

铜绿假单胞菌

, and

,以及

Streptococcus pyogenes

化脓性链球菌

. Recognizing how large a role the host plays a role in the evolution of antibiotic resistance, the researchers plan to perform similar studies in patients undergoing chemotherapy and recent transplant recipients to see if those populations are also prone to antibiotic-resistant infections.

认识到宿主在抗生素耐药性演变中的作用有多大,研究人员计划对接受化疗的患者和最近的移植受者进行类似的研究,看看这些人群是否也容易出现抗生素耐药性感染。

News

新闻

Bacterial diseases

细菌性疾病

Diabetes

糖尿病

Mice

老鼠

Microbial drug resistance

微生物耐药性

Staphylococcus

葡萄球菌