It is amazing to know that how innate immune proteins are not prone to bacterial resistance. I have created this chat in order to have your thoughts and views on this topic.
The innate immune system actually has a great deal of diversity associated with its responses to a pathogen. Importantly, this included communication with the adaptive immune response. For instance, the presence of antibody on the surface of a bacteria is a signal for the that bacteria to be phagocytosed. In this way the attempts to develop resistance to this mechanism of immunity would be thwarted by the development of antibodies against alternative epitopes on the same bacteria which would be called epitope spreading.
The second aspect which I think is largely the main point of your question is how Pathogen Associated Molecular Patterns (PAMPs) have not been selected against or altered such that the innate immune response cannot recognize them. I think that an important aspect of this is that the patterns themselves are fundamental components of what it means to be a living microbe. For instance, Mark mentioned that DNA can serve as a molecular pattern that activates the innate immune response (although this is can be a Damage Associated Molecular Pattern or a PAMP). So lets be very specific; say that we are talking about cytoplasmic dsDNA such as you would find in the case of a viral infection. In this case the Cytoplasmic DNA would stand out as suspicious molecular pattern which would be recognized by a toll-like receptor and stimulate interferon production by the infected cell. In this case for the the virus or whatever is the sources of the Cytoplasmic DNA to avoid detection and ultimately activation of signaling downstream of a pattern recognition molecule (PRM), it would have to change a fundamental feature of itself. One might consider that this virus could change its genetic material from DNA to RNA to avoid detection via this same, but this seems like a tall order. We can consider other PAMPs such as LPS or lipoteichoic acids, but these too are fundamental components of bacterial membranes and to change/loose these is a monumental biochemical task. I would not dare say that this is impossible, but I do think that for it to happen, a great deal of time and a very consistent selective pressure would be required and immune systems of higher organisms provide neither.
Yet another aspect to consider is that while it may be possible to change a single very important component of a bacteria or a virus, the innate immune response has an entire array of receptors that recognize a multitude of components of viruses and bacteria. So while gaining resistance to innate immune response initiated by a single PRM may be possible preventing innate immune response mediated by all PRMs would in many ways change the current conceptualization of the narrow constraints in which we recognize that life can exist. While this is an interesting point and possibly an important consideration, I am not enough of an expert on the subject to determine if resistance / loss of all patterns recognized by the innate immune system would be required for a selective advantage or if the loss of a single molecule would be sufficient. I would be happy to hear other peoples thoughts.
Finally we have to consider the fact that even though higher organisms have a whole host of mechanisms through which they can fight infection, infectious agents persist to cause infections in higher organisms and importantly the infections agents present many of the patterns already discussed here. So, it is not strictly necessary that bacteria develop resistance to these mechanisms through the loss of the pattern/s. One can go further to consider that several organisms actually can actually capitalize on activation of the innate immune system. So if this would be an example of the resistance that you asked about then the answer to your question is that they do. If on the other hand if you consider resistance to mean the loss of a molecular pattern, then I think a major component of the answer is that the patterns recognized are so fundamental to the cell that changing or losing those components while maintaining life is a monumental evolutionary task.
My understanding is that dhe Innate Immune Response (IIR) is activated by endogenous DNA or dsRNA. For instance, type I interferons are activated by the recognition of dsRNA pathogen dsDNA or mtDNA, which then causes STING to activate TBK1 leading to the activation of the type I interferons.
If I am reading your question properly, you want to know why this pathway also doesn't recognize bacterium. The IIR pathway recognizes nucleic acids. Bacterium do not have their nucleic acids exposed during infection to the cell. For instance, Salmonella invades via a secretion system that enables the bacteria to remodel the host cell membrane and create a salmonella containing vacuol (SCV). In such an instance, the bacteria is not exposed to the sensor components of the IIR, which are only sensitive to nucleic acids. Rather, the cell makes use of MHC to sense pathogen associated mebrane proteins (PAMPs) on the surface of the bacterium. This is a pathway completely separate from the IIR, which is why the IIR is not stimulated by bacterium.
The innate immune system actually has a great deal of diversity associated with its responses to a pathogen. Importantly, this included communication with the adaptive immune response. For instance, the presence of antibody on the surface of a bacteria is a signal for the that bacteria to be phagocytosed. In this way the attempts to develop resistance to this mechanism of immunity would be thwarted by the development of antibodies against alternative epitopes on the same bacteria which would be called epitope spreading.
The second aspect which I think is largely the main point of your question is how Pathogen Associated Molecular Patterns (PAMPs) have not been selected against or altered such that the innate immune response cannot recognize them. I think that an important aspect of this is that the patterns themselves are fundamental components of what it means to be a living microbe. For instance, Mark mentioned that DNA can serve as a molecular pattern that activates the innate immune response (although this is can be a Damage Associated Molecular Pattern or a PAMP). So lets be very specific; say that we are talking about cytoplasmic dsDNA such as you would find in the case of a viral infection. In this case the Cytoplasmic DNA would stand out as suspicious molecular pattern which would be recognized by a toll-like receptor and stimulate interferon production by the infected cell. In this case for the the virus or whatever is the sources of the Cytoplasmic DNA to avoid detection and ultimately activation of signaling downstream of a pattern recognition molecule (PRM), it would have to change a fundamental feature of itself. One might consider that this virus could change its genetic material from DNA to RNA to avoid detection via this same, but this seems like a tall order. We can consider other PAMPs such as LPS or lipoteichoic acids, but these too are fundamental components of bacterial membranes and to change/loose these is a monumental biochemical task. I would not dare say that this is impossible, but I do think that for it to happen, a great deal of time and a very consistent selective pressure would be required and immune systems of higher organisms provide neither.
Yet another aspect to consider is that while it may be possible to change a single very important component of a bacteria or a virus, the innate immune response has an entire array of receptors that recognize a multitude of components of viruses and bacteria. So while gaining resistance to innate immune response initiated by a single PRM may be possible preventing innate immune response mediated by all PRMs would in many ways change the current conceptualization of the narrow constraints in which we recognize that life can exist. While this is an interesting point and possibly an important consideration, I am not enough of an expert on the subject to determine if resistance / loss of all patterns recognized by the innate immune system would be required for a selective advantage or if the loss of a single molecule would be sufficient. I would be happy to hear other peoples thoughts.
Finally we have to consider the fact that even though higher organisms have a whole host of mechanisms through which they can fight infection, infectious agents persist to cause infections in higher organisms and importantly the infections agents present many of the patterns already discussed here. So, it is not strictly necessary that bacteria develop resistance to these mechanisms through the loss of the pattern/s. One can go further to consider that several organisms actually can actually capitalize on activation of the innate immune system. So if this would be an example of the resistance that you asked about then the answer to your question is that they do. If on the other hand if you consider resistance to mean the loss of a molecular pattern, then I think a major component of the answer is that the patterns recognized are so fundamental to the cell that changing or losing those components while maintaining life is a monumental evolutionary task.
I think that the microbes do generate resistance to innate immune response.
You may find the answer to this under a slightly different terminology and that is called the evasion of innate immunity.
In fact only the microbes which are successful in evading the innate immunity end up becoming pathogenic.
The fact that the innate immunity consist of a variety of mechanisms including the physicochemical barriers to antimicrobial peptides, complements, PAMP receptors, interferon, Oxidative/nitrosative radicals etc, it is difficult for microbes to generate evasive mechanisms to each and every one of these. And that's why most microbes that we encounter cannot manifest pathogenesis. However, some become successfull in evading most or all of these mechanisms and become causative agents of various diseases.